Category Archives: Genome

As the Covid-19 virus (coronavirus SARS-CoV-2) continues to spread and claim victims worldwide, its origins remain unknown. Each scientific community puts forward its own theory, with some suggesting the virus may have leaked out of a laboratory.

Another theory, based on recent studies of the Wuhan wet market in China, along with others carried out in Cambodia, Laos, Japan, China, and Thailand, posits that an ancestral virus in rhinolophus bats went on from infecting wild and/or domestic animals to humans. Indeed, in these different studies, several viruses with genetic sequences very similar to SARS-CoV-2 were isolated in these bats.

Though it has been shown some bat species have hosted these coronaviruses naturally, the wild or domestic animal (or animals) that acted as a bridge between them and humans the missing link remains unidentified. Pangolins were first suspected, but now appear to have been collateral victims rather than one of these much-talked-about missing links. A coronavirus genome sequence detected in pangolins was indeed related to that of SARS-CoV-2, but the rest of the genome was too distant from it genetically to back the hypothesis.

Moreover, the pangolins hosts in which the viruses that were genetically close to SARS-CoV-2 were found had mostly been confiscated at live-animal markets, at the end of the supply chain. As a result, they had been in lengthy contact with other animal species. It is very likely they were infected along this supply chain rather than in their natural environment. Mink farms were also suspected of being an intermediate host in China.

Lastly, pangolins and rhinolophus bats do not share the same habitat, making it highly unlikely there was any contact between the two species in which the virus jumped from one to the other. On the other hand, civets and raccoon dogs could be an intermediate source of SARS-CoV-1). Rodents or primates could also carry pathogens with zoonotic potential, such as hantaviruses which can cause haemorrhagic fever with renal syndrome or filoviruses, which include the Ebola virus. The latter is passed on to humans through wild animals, in particular bats, antelopes, and primates such as chimpanzees and gorillas, then spreads among humans, mainly by direct contact with blood, secretions and other bodily fluids from infected people. The average case fatality rate is around 50%.

In 2013, initial cases of disease from the Ebola virus were detected in West Africa. The rise of these cases led to over 10,000 deaths, mainly in Guinea, Liberia, and Sierra Leone.

Activities such as hunting, animal-handling or eating meat from wild animals therefore create the conditions for viruses to spread from animals to humans a potentially devastating phenomenon called spillover.

The ZooCov project has sought to define and quantify this risk in Cambodia. For almost two years and right from the start of the pandemic it has adopted a One Health approach to explore whether and how pathogens such as coronaviruses can be passed on to humans from wild animals that are hunted and eaten.

Indeed, in South-East Asia, wild animals are regularly traded, and bushmeat is customarily eaten. This eating habit is often opportunistic. In some communities, it complements a low-protein diet. It can also be frequent and targeted. In Cambodia, 77% of 107 families interviewed in the ZooCov project said they had eaten bushmeat in the past month.

Use for medicinal purposes is also widespread. In Vietnam, an analysis of records of the Vietnamese authorities confiscating pangolins and related by-products between 2016 and 2020 reported 1,342 live pangolins (6,330 kg), 759 dead pangolins or pangolin carcasses (3,305 kg), and 43,902 kg of pangolin scales.

Yet this consumption also has a cultural and social dimension that is still not properly understood. Among the well-off and often in big cities people sometimes eat bushmeat out of a desire for social status, and a belief that eating it endows them with the physical or physiological attributes of the animal. They also sometimes eat bushmeat out of rejection of industrially produced meat, considered unhealthy. Animals are widely reared to meet this demand and the demand for fur production.

In the Stung Treng and Mondolkiri provinces of Cambodia, where protected forest areas remain, researchers surveyed more than 900 people living on the edge of these forests to determine the structure of the illegal bushmeat trade. Statistical analyses are underway to identify the people most at risk of contact with wildlife thus with such pathogens. We already know those exposed are mostly young middle-class men, and that some communities are more exposed than others. Sociological studies have also helped better grasp todays context: the legal framework, the profiles of players in the trade, their motives and deterrents in trade and consumption of wild animals, and how the context has changed with each different health crisis (bird flu, Ebola, SARS-CoV-1, etc.).

These successive crises seem to have scarcely affected the habits of these communities. Beyond regularly eating bushmeat, one fourth of the families surveyed said they still hunted or ensnared wild animals, and 11% claimed to sell bushmeat or wild animals. Furthermore, in the same areas of study, over 2,000 samples taken from wild animals trafficked or eaten for subsistence bats, rodents, turtles, monkeys, birds, wild pigs, etc. were analysed. Some of these samples tested positive for coronaviruses and scientists at the Institut Pasteur du Cambodge (IPC) are currently sequencing their genome in a bid to learn more about their origin, evolution, and zoonotic potential. Finally, researchers collected blood samples from over 900 people from the same region to find out whether they had been in contact with a coronavirus or coronaviruses. These analyses are still underway, but what we do know is that these people had not been exposed to SARS-CoV-2 when the survey was conducted.

If the Covid crisis has taught us anything, it is the importance of detecting such emergences early in order to nip the pathogens in the bud. While many questions remain about the way cases emerge, there are just as many questions about the monitoring systems that should be set up to track them. The results of the ZooCov project will be used to develop a system for detecting spillover of zoonotic viruses early, particularly by strengthening the system for monitoring wildlife health that is already in operation in Cambodia, which was set up by the Wildlife Conservation Society (WCS). Other large-scale projects in research and development will help us understand, detect, and prevent these phenomena of emerging cases.

The authors would like to thank Cambodias Ministry of Health, its Ministry of Agriculture, Forestry and Fisheries, and its Ministry of Environment, as well as all the projects partners: Institut Pasteur du Cambodge (IPC), the Wildlife Conservation Society (WCS), Flora and Fauna International (FFI), Institut de Recherche pour le Dveloppement (IRD), Hong Kong University (HKU), the GREASE network, International Development Enterprise (iDE), the World Wildlife Fund (WWF), Elephant Livelihood Initiative Environment (ELIE), BirdLife International, Jahoo, and World Hope International.

Translated from the French by Thomas Young for Fast ForWord.

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On the trail of the origins of Covid-19 - The Conversation

An international team of researchers, including one from The University of Western Australia, has successfully unravelled the genomes of 418 unique samples of rapeseed from across the globe to identify traits that breeders can use to improve crop yield.

The study Genomic selection and genetic architecture of agronomic traits during modern rapeseedBreeding published in Nature Genetics, follows a four-year collaboration between the scientists from Australia, China and the United States.

Professor Jacqueline Batley, from UWAs School of Biological Sciences and The UWA Institute of Agriculture, who is an author on the paper, said that rapeseed, known as canola in Australia, is the second most important oil-producing crop worldwide.

Which means that breeders are looking at ways that they can generate plants with the desired characteristics or traits that will allow them to minimise crop losses and maximise crop yields, Professor Batley said.

While the adaption, yield and quality of canola have all considerably improved in recent decades due to intensive breeding the genetics underlying desirable traits such as the architecture of the plant, seed weight and oil content have remained unclear because these are controlled by multiple genes.

Working together, the research team unravelled the genomes of 418 diverse rapeseed accessions from different geographical locations representing global genetic diversity. In doing so, they were able to identify the genes behind 56 traits that were modified during rapeseed improvement.

This provided us with insights into the genetic control of these important traits, Professor Batley said.

Taken together, our study revealed a landscape of genomic variation for diverse varieties and artificial selection or adaptation during rapeseed breeding. The results are a real insight into the make-up of rapeseed and should help accelerate future breeding for crop improvement.

Professor Batley said the complex genetic sequencing generated in the ground-breaking study will not only be an indispensable resource for genome-assisted rapeseed breeding but also a valuable database for other scientists conducting research on rapeseed.

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Unravelling the genetic keys to improve canola crop yield - University News: The University of Western Australia

In Nature News, Smriti Mallapaty describes the ethical debate surrounding care for the twin girls whose birth was reported by genome editing researcher He Jiankui.

He, who was jailed for his research, claims to have used CRISPR-Cas9-based gene editing to edit the CCR5 gene in twin embryos that were implanted in a woman who gave birth in 2018. A third genome-edited baby was born to other parents. CCR5 codes for a protein that HIV uses to make its way into human cells.

Two Chinese bioethicists would like to see a research center "dedicated to ensuring the well-being of the first children born with edited genomes," Mallapaty explains, though other experts "are concerned that the pair's approach would lead to unnecessary surveillance of the children."

While no other genome-edited babies have been reported, likely owing to He's punishment and backlash to the work in the scientific community, interest in the approach has persisted, she explains. In the meantime, experts are grappling with bioethical and practical issues surrounding the genome-edited children from their medical care and health testing to the potential social and psychological effects of their experience.

"Researchers say that the latest proposal, in a document by Qiu Renzong at the Chinese Academy of Social Science in Beijing and Lei Ruipeng at the Huanzhong University of Science and Technology in Wuhan, is the first to discuss how to manage the children's unique situation," Mallapaty writes. Among their recommendations, the pair calls for "regular sequencing of the children's genomes to check for 'abnormalities,' including conducting genetic tests of their embryos in the future."

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Think of the Children? | Genomeweb - GenomeWeb

OverviewCGView is a Java package for generating high quality, zoomable maps of circular genomes. Its primary purpose is to serve as a component of sequence annotation pipelines, and as a means of generating visual output suitable for the web. Feature information and rendering options are supplied to the program using an XML file or a tab-delimited file. CGView converts the input into a graphical map (PNG, JPG, or SVG format), complete with labels, a title, legends, and footnotes. In addition to the default full view map, the program can generate a series of hyperlinked maps showing expanded views. The linked maps can be explored using any web browser, allowing rapid genome browsing, and facilitating data sharing. The feature labels in maps can be hyperlinked to external resources, allowing CGView maps to be integrated with existing web site content or databases. For examples of the various output types, see the CGView gallery.

In addition to the CGView application, an API is available for generating maps from within other Java applications, using the cgview package.

CGView can be used for any of the following:

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CGView - Overview

Pacific Biosciences of California, Inc.

SickKids will use HiFi Sequencing to explore potential genetic causes of a range of medical and developmental conditions

MENLO PARK, Calif., Feb. 28, 2022 (GLOBE NEWSWIRE) -- PacBio, a leading provider of high-quality, highly accurate sequencing platforms, today announced it will be supporting The Hospital for Sick Children (SickKids) in Toronto, Canada in using HiFi whole genome sequencing (HiFi WGS) to potentially identify genetic variants that may be associated with medical and developmental conditions. Samples that will be examined using HiFi WGS were previously sequenced using short-read DNA sequencing technology, but still lack the identification of a disease-causing variant.

Even though more than 70 percent of rare disease, autism and intellectual disability have genetic causes, more than 50 percent lack an identified causative genetic alteration despite the use of microarrays, whole-exome or short-read whole-genome sequencing (srWGS).

SickKids will use HiFi WGS to analyze samples from research participants who are highly suspected to have a genetic condition but have not yet received a diagnosis despite previous genetic testing, including srWGS. The team will explore whether HiFi WGS can detect potential genetic causes for a range of conditions, such as autism spectrum disorder and congenital diseases.

HiFi sequencing allows us to investigate the entire genome in a way that is not accessible with other technologies, said Dr. Christian Marshall, Clinical Laboratory Director, Genome Diagnostics and Associate Director at The Centre for Applied Genomics (TCAG) at SickKids. We hope HiFi sequencing will enable us to take an exploratory look at classes of variation and large sections of the genome that were not detected previously, potentially showing unidentified causative genomic variants in these samples.

PacBios technology has been used to help genetic disease researchers explain mysteries where other technologies could not, said Edd Lee, Director of Human Genomics at PacBio. We are excited to support the SickKids team to hopefully uncover the answers they have been seeking.

Story continues

To learn more about the benefits of HiFi WGS in genetic disease, visit http://www.pacb.com/rare-disease.

About PacBioPacific Biosciences of California, Inc. (NASDAQ: PACB) is empowering life scientists with highly accurate sequencing platforms. The companys innovative instruments are based on Single Molecule, Real-Time (SMRT) Sequencing technology, which delivers a comprehensive view of genomes, transcriptomes, and epigenomes, enabling access to the full spectrum of genetic variation in any organism. Cited in thousands of peer-reviewed publications, PacBio sequencing systems are in use by scientists around the world to drive discovery in human biomedical research, plant and animal sciences, and microbiology. For more information, please visit http://www.pacb.com and follow @PacBio.

PacBio products are provided for Research Use Only. Not for use in diagnostic procedures.

Forward-Looking Statements This press release may contain forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and the U.S. Private Securities Litigation Reform Act of 1995, including statements relating to future availability, uses, accuracy, advantages, quality or performance of, or benefits or expected benefits of using, PacBio products or technologies; the suitability or utility of such products or technologies for particular applications or projects, including in connection with the SickKids collaboration; potential increases in variant detection and providing answers for rare disease samples, in the SickKids collaboration in particular and rare disease research in general; and other future events. Readers are cautioned not to place undue reliance on these forward-looking statements and any such forward-looking statements are qualified in their entirety by reference to the following cautionary statements. All forward-looking statements speak only as of the date of this press release and are based on current expectations and involve a number of assumptions, risks and uncertainties that could cause the actual results to differ materially from such forward-looking statements. Readers are strongly encouraged to read the full cautionary statements contained in the Companys filings with the Securities and Exchange Commission, including the risks set forth in the companys Forms 8-K, 10-K, and 10-Q. The Company disclaims any obligation to update or revise any forward-looking statements.

Contacts

Investors: Todd Friedmanir@pacb.com

Media:Lizelda Lopezpr@pacb.com

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PacBio Supports SickKids to Investigate Use of HiFi Sequencing in Undiagnosed Genetic Conditions - Yahoo Finance

Genomic sequencing has been a key tool throughout Aotearoas COVID-19 pandemic, with data generated here now part of the 8.5 million genomes shared globally.

It has helped us understand how cases arrived here and the extent of community outbreaks. It has also given us detailed insight into how the virus is transmitted from person to person, on a plane or quarantine facility.

As Omicron spreads rapidly across the country, it is important to consider how we best deploy genomics to achieve our public health goals. Which cases should we sequence and why? What is the role of wastewater when we know cases are already in our cities and regions?

Even as our testing and genomics capacity gets overwhelmed by the sheer number of cases, sequencing will continue to play an important role.

Firstly, we need to keep an eye open for new viral variants and keep track of those already circulating in the community. This is a core role of genomic surveillance and part of a global effort, with scientists around the world sequencing variants in their backyard.

Read more: How COVID-19 transformed genomics and changed the handling of disease outbreaks forever

One thing we are looking for is changes (mutations) in the virus that may affect its ability to transmit, evade our vaccines or immune defences, or cause even more serious disease. Particular scrutiny is given to mutations in the viral spike protein, on the outside of the virus, which allows it to latch onto cells and infect them.

The Pfizer vaccine we have used in Aotearoa essentially presents the body with a copy of the spike protein to train the immune system to create antibodies and other defences against it. Major changes in the spike might allow the virus to evade at least the first line of our immune defences as we have seen with the Omicron variant, which contains more than 30 different mutations in the spike protein.

With relatively few cases overall in New Zealand, and only the Delta variant that has persisted in the community for more than a few months, we have so far not seen any concerning new mutations or variants arise here. But small mutations or deletions in the viruss genetic code remain helpful for linking clusters and detecting new introductions into the community.

The majority of New Zealanders are now vaccinated, which means there is increasing pressure on the virus to escape our immunity. This is an arms race we have been playing with viruses for millennia. The game has changed somewhat as genomics allows us to watch viral evolution in real time.

By sequencing the virus from individual cases, we can tell exactly which variant the person has and, over time, we can detect patterns of variants rising in frequency or resulting in a more severe infection.

Currently, genomic surveillance tells us there is a mix of Omicron (including major variants BA.1, and BA.2) and a stubborn tail of Delta.

The BA.1 lineage was given an early boost at a wedding-related super-spreading event and now makes up 74% of Omicron cases. The remaining 26% of Omicron cases are BA.2 which was spread early on at the SoundSplash festival. In the last week, about 7% of cases sequenced were Delta. Without sequencing, we would be blind to this.

To maintain high-quality surveillance in the face of very high case numbers, we need to be selective in which samples we sequence and balance competing priorities.The top priority is the prevention of severe disease and there will be a focus on the genomes of cases in hospital. Overseas, many of the serious, hospitalised cases are Delta, not Omicron.

Some patients may have the misfortune of chronic COVID-19 infections. In such cases, multiple samples may be sequenced to see if the virus is changing within a single patient.

A leading hypothesis of how variants of concern such as Omicron and Delta have emerged is via chronically infected patients who act as an incubator for the virus. We need to continue monitoring patients with long-haul COVID.

We will also need to continue to monitor and sequence new cases that arrive at the border, either in MIQ or in recently returned travellers who test positive. Nearly all the genetic variation of SARS-CoV-2 we have seen in Aotearoa has been imported (as opposed to developed here), and this is a common pattern we see with other diseases such as influenza. By sequencing border cases, we get an early view of what we may need to prepare for.

Read more: Genomic sequencing: Here's how researchers identify omicron and other COVID-19 variants

Finally, to get a high-level view of cases and mutations, we sequence a random sample of cases across the country. Genomic sequences taken across time and space build a picture of which parts of the country are host to which variants and lineages. It is very much a case of know thy enemy.

Currently we are monitoring the areas where Delta is persisting. We can also monitor how the vaccine status of an individual affects the variant that is detected. Such data helps to build a picture of vaccine efficacy and population-level protection against a fast-changing virus.

The last piece of the genomic sequencing puzzle is wastewater testing for SARS-CoV-2. While sequencing from wastewater samples has been used for specific public health investigations in the past, low case numbers and quantities in most wastewater samples has made it difficult. Instead, wastewater testing has focused on using a sensitive method to allow for the early detection of the virus.

With the Omicron surge, we are now seeing an increase in both the number of positive wastewater samples and the amount of virus in those samples. This means we can use wastewater to indicate increasing or decreasing trends in cases at community level, and also to monitor known and new variants through sequencing and other tools.

In the weeks to come, there will be enough viral matter to make trends in wastewater data evident. In some cities, where regular sampling occurs, we will see viral wastewater loads trending up and down with case numbers. This information, along with regular case reporting, will inform the public about the relative risk of various regions. Such data may help people to understand the risks of travelling to a certain region or city.

Genomics remains a key tool in our pandemic management. There will be changes in how we use it, but it remains a core part of our surveillance toolkit. Prior to the genomics era, changes in the viral genetic blueprint were invisible to us. While many will dread another story about a new variant, we would be in a far worse position without this information.

If we step outside of our COVID-19 bubble for a second, the use of fast and affordable genomic technology in this pandemic also provides a glimpse of what genomic medicine may look like in the future but that is a discussion for another day.

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As New Zealand's Omicron infections rise rapidly, genome surveillance is shifting gears - The Conversation AU

by Dr Firoz AhmadThe landmark completion of the human genome project in 2003 and its subsequent refinement has undoubtedly marked the beginning of a new era for biomedical research. The human genome project helped us to understand the most accurate sequence of the 3 billion DNA base pairs that make up the human genome. With this development, we have witnessed a paradigm shift in which medicine became personalized, predictive and preventive especially in fatal disease like cancer and other chronic diseases. There has been growing interest in expanding these success stories to Rare diseases (RDs), which are often progressive, frequently devastating and life-threatening clinical conditions. Although RDs affect a limited fraction of individuals from the general population (1 in 5000 people or less in Indian context), in aggregate they represent a substantial challenge to global health systems.There are approximately 5,000 to 8,000 different rare diseases globally, and it comes in many forms and includes some cancers, auto-immune diseases, metabolic conditions, blood disorders, neurological disorders and inherited malformations. Available literature suggests that India is home to nearly 70 million affected people with rare diseases, and some of the common examples are primary immunodeficiencies, hemoglobinopathies, muscular dystrophies, Lysosomal storage disorders, Niemann-Pick Disease, Ethylmalonic Encephalopathy, familial hypercholesterolemia, Mucopolysaccharidoses type I and type II, Rhizomelic chondroplasia punctata type 1, pseudorheumatoid dysplasia, ichthyosis, dystrophic epidermolysis bullosa, sporadic acrokeratosis, Tay-Sachs disease, Von Willebrand disease, Werner syndrome, Spastic Paraplegia 79 and many more. Majority of these diagnosed RDs are so rare that it is extremely difficult to identify clinically, patient may need 7-8 medical consultations, and at times it takes several years to come to conclusive diagnosis (Fig-1). As far as the etiology of the RDs is concerned, the exact cause for many rare diseases remains unknown. Still, for a significant portion, the problem can be traced to mutations in a single gene (genetic origin).As these conditions are tough to recognize clinically, genetic and genomic testing have become the backbone of diagnostic modality in recent times. Identification of pathogenic DNA changes remained a big challenge in earlier days (late 70s), wherein basic information about the DNA sequence and genomic location of a abnormal gene had to be worked out through a tedious, time consuming and expensive laboratory process called cloning followed by first generation sanger sequencing of the cloned product. Technological progress in DNA sequencing spurred after 2003, with the introduction of first high-throughput sequencing (Next Generation Sequencing, NGS) technology by Roche in 2005, capable of detecting genetic variation with high precision and accuracy. In no time, NGS became the true game-changer and brought a complete Genome Revolution by offering the capability to read the entire genomes, rather than individual genes. This gave researchers the ability to identify potential disease-causing variants across the genome much more rapidly than had previously been possible. Last one and half decade has seen rapid progress in the NGS technologies in terms of sequencing chemistry, data output, longer read lengths and improved bioinformatics tools. This has significantly increased the outputs of sequencing data in the gigabase range per instrument run, resulted in much affordable cost compared to the traditional Sanger first-generation sequencing method, and at a much quicker pace. Today, broader multigene panels (checks few clinically relevant genes), whole exome sequencing (checks all the coding exons of the genome, WES), clinical exome sequencing (checks approx. 6000 genes known to cause human diseases, CES), and whole genome sequencing (checks all exons and non-coding regions of the genome, WGS), are the most preferred testing methodologies in RD diagnosis. Patients are now increasingly liberated from the long-standing diagnostic bottleneck. Many can receive a diagnosis in just 2-3 months using modern day genomics tools in comparison to 7-8 years of traditional way, with a precision that remains unparalleled in medicine.

Generally a referring doctor considers high end genomic testing, if a patient visits to his/her clinic with non-specific overlapping symptoms and unexplained illness, or known to have several affected family members, or couples who have undergone consanguineous marriage. Furthermore, many paediatricians prefer to do genomics testing if they see early disease onset in a child or repeated episodes of seizures in newborn babies. As depicted in (Fig-1), the strategy begins with collection of detailed clinical information of the patient and his/her family history. Based on the clinical suspicion and past knowledge on the molecular etiology of the suspected disorders, two different approaches are considered for the genetic screening. In case of clinically suspected but genetically characterized RDs, screening of known disease-associated candidate genes through a multigene targeted panel or Clinical exome based NGS approach is recommended.

Thanks to this recent technological advance in genomics, the number of Mendelian diseases that have a known genetic cause went from 1,257 in 2001 to 4,589 in 2022 . The Genome Revolution has opened the door for true personalization in disease management, and it is now truly improving peoples health. With several success stories emerging globally including India, genomics will become a mainstay for diagnosis of rare genetic diseases in the near future.

by Dr Firoz Ahmad, Section-Head, Molecular Pathology, SRL Diagnostics, Mumbai

(DISCLAIMER: The views expressed are solely of the author and ETHealthworld does not necessarily subscribe to it. ETHealthworld.com shall not be responsible for any damage caused to any person / organisation directly or indirectly.)

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Massive Scale Genome Revolution: Changing the Rare Diseases Landscape - ETHealthworld.com

SAN FRANCISCO--(BUSINESS WIRE)--Serotiny, a leader in high-throughput therapeutic Multi-Domain Protein (tMDP) engineering, and Tessera Therapeutics, a biotechnology company pioneering a new approach in genetic medicines known as Gene Writing technology, today announced a collaboration to engineer programmable Gene Writer proteins. This collaboration will build on Tesseras innovations in genome engineering technologies and apply Serotinys tMDP mining and design expertise to further optimize Tesseras programmable Gene Writer proteins, capable of making diverse and directed alterations to the genome.

Were extremely excited to be working with the Tessera team, said Colin Farlow, J.D., Serotinys CEO. It provides Serotiny a unique opportunity to extend the validation of our platform and to continue to advance our efforts in discovering and developing proteins with novel function for the purpose of enhancing the therapeutic utility of next-generation genetic medicines.

Tesseras Gene Writer candidates can allow the substitution, insertion, or deletion of DNA sequences, as well as the writing of entire genes into the genome, offering the potential for a new category of genetic medicines. By partnering with Serotiny, Tessera will have the ability to identify, screen, and optimize a variety of proteins that can serve as the foundation of future Gene Writer therapies across a variety of disease states.

Tesseras mission is to cure disease by writing in the code of life and were committed to continuously innovating to improve and expand our Gene Writing platform, said Geoffrey von Maltzahn, PhD, co-founder and CEO of Tessera. Our R&D engine seeks to learn from billions of years of mobile genetic element evolution to generate novel Gene Writing systems with the ability to solve important challenges in genetic medicine. Serotinys multi-domain engineering expertise has the potential to further optimize our Gene Writer protein libraries and were delighted to partner with the Serotiny team.

Under terms of the agreement Serotiny will receive an upfront payment and is eligible for certain future consideration, contingent upon the collaboration achieving pre-specified performance thresholds.

About Serotiny

Serotiny is a pre-clinical discovery company building better gene and cell therapies through high-throughput engineering of therapeutic Multi-Domain Proteins (tMDP) such as Chimeric Antigen Receptors (CARs), CAR alternatives, accessory proteins, and next generation gene editors. At the heart of Serotinys technology is a discovery platform that harmonizes computationally aided protein design, high-throughput cellular assays, and next generation sequencing. Serotinys platform enables a cross disciplinary approach to engineering large and often unstructured multi-domain proteins, applying expertise from synthetic biology, immunology, machine learning, software engineering and bioinformatics. For more info visit http://www.serotiny.bio, or contact Colin Farlow at info@serotiny.bio.

About Tesseras Gene Writer platform

Tesseras Gene Writer proteins are based on natures genome architects, Mobile Genetic Elements (MGEs)the most abundant class of genes across the tree of life, representing approximately half of the human genome. Tessera has evaluated tens of thousands of natural and synthetic MGEs to create Gene Writer candidates in multiple categories including:

Tesseras research engine further optimizes the discovered Gene Writer candidates for efficiency, specificity, and fidelityessentially compressing eons of evolution into a few months.

About Tessera Therapeutics

Tessera Therapeutics is pioneering Gene Writing technology, which consists of multiple technology platforms designed to offer scientists and clinicians the ability to write therapeutic messages into the human genome, thereby curing diseases at their source. The Gene Writing platform allows the correction of single nucleotides, the deletion or insertion of short sequences of DNA, and the writing of entire genes into the genome, offering the potential for a new category of genetic medicines with broad applications both in vivo and ex vivo. Tessera Therapeutics was founded by Flagship Pioneering, a life sciences enterprise that conceives, resources, and develops first-in-category bioplatform companies to transform human health and sustainability. For more information about Tessera, please visit http://www.tesseratherapeutics.com.

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Serotiny and Tessera Therapeutics enter into collaboration to engineer and optimize programmable Gene Writer proteins - Business Wire

Ketterson was trained and worked under the direction of Dr. Jacques Cohen and Dr. Mina Aliknai from 1996-2004 at The Institute for Reproductive Medicine and Science at Saint Barnabas Medical Center and alongside Dr. Santiago Munn in the development of embryo biopsy and PGT as a reference laboratory test.She is a highly experienced clinical embryologist specializing in embryo biopsy techniques, routine IVF procedures, quality control, clinical research trials and laboratory operations.

"I have had an incredible career and I thought it could not get any better until I received Dr. Treff's call asking me to join his team at Genomic Prediction," said Ketterson."Everything about my position on this team, their passion to improve reproductive genetic care for IVF patients and the warm welcome I have received is positioned to be the highlight of my tenure in reproductive health."

Ketterson has also served as the Executive Director for several educational conferences specializing in the continuing education of reproductive endocrinologists, IVF nurses, embryologists, andrologists and administrative staff. She has traveled throughout the world performing embryo biopsy procedures, improving laboratory standards and teaching micromanipulation techniques.

Prior to her role with Genomic Prediction and Cooper Surgical, Ketterson was the Chief Operating Officer Reprogenetics, Executive Director of Tyho-Galileo Research Laboratories and Althea Science.She has also completed the Master's Program in Biomedical Science at the Jones Institute at Eastern Virginia Medical School in Norfolk, Virginia.

Ketterson is passionate about the IVF field and her experience includes R&D in the area of IVF products and services, co-founding companies in the genomics space as well as development of web applications to improve the quality control in the IVF laboratory. She regularly participates with RESOLVE in their annual events to bring an understanding of infertility, IVF procedures and access to care for patients needing IVF services. Ketterson has served on both the ASRM exhibitor committee and the ESHRE genomics working group.

"We are so pleased that Kelly is joining our team," said Chief Science Officer and co-founder of Genomic Prediction, Dr. Nathan Treff. "Her years of experience combined with her real passion for improving the industry on behalf of patients is second to none."

Genomic Prediction CEO, Laurent Christian Asker Melchior Tellier echoed Treff's sentiment saying "a true pro, we are thrilled that Kelly brings her collaborative spirit and deep knowledge to the Genomic Prediction family."

About Genomic Prediction

Genomic Prediction is redefining human embryo genetic testing through ultra high resolution genetic reports so that, for the first time in human history, prospective parents can protect their future children from inheriting a predisposition to the most common diseases. Genomic Prediction's LifeView testing platform screens for diseases such as diabetes, heart disease, schizophrenia, and common cancers. We provide parents undergoing In Vitro Fertility treatments (IVF) with the means to reduce the risk to their embryos of chromosomal abnormalities, and other heritable diseases. Backed by rigorous preclinical validation and a unique interdisciplinary approach that combines years of experience in molecular genetics and computational biology, LifeView provides a one-of-a-kind machine learning based prediction of genetic abnormalities. Learn more about Genomic Prediction's LifeView testing at http://www.lifeview.com

Media contact: Elizabeth CarrCommunications Director, Genomic Prediction[emailprotected] 617.791.0163.

SOURCE Genomic Prediction

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Kelly Ketterson joins Genomic Prediction Team as Chief Operating Officer - PRNewswire

As repetitive as I have been with respect to this, there is nothing new under the sun when it comes to antivaccine myths, misinformation, and disinformation, and that applies to COVID-19 vaccines. If public health officials and messengers had paid more attention to the tactics and tropes of the antivaccine movement, including its central conspiracy theory, maybe they would have been more prepared for the onslaught of antivaccine misinformation that was unleashed as the mRNA COVID-19 vaccines were undergoing clinical trials and when they were finally initially approved under an emergency use authorization (EUA) near the end of 2020. They didnt, and here we are, which is why, having seen it before multiple times last year, Im faced with the return of the revenge of the antivaccine lie that mRNA-based COVID-19 vaccines permanently alter your DNA (they dont, nor do they hack the software of life, nor are they really gene therapy) this time from Jessica Rose, who is affiliated with James Lyons-Weilers antivaccine institute with the humble name of Institute for Pure and Applied Knowledge (IPAK). Unfortunately, Saturday I saw this zombie lie resurrected yet again in the form of an article on Substack (where the cranks whove been banned from Twitter, Facebook, YouTube, etc. all go) by Rose titled It does incorporate into human DNA. And its probably messing up embryogenesis, subtitled, These injectable convid-1984 products are perfect bioweaponseither by design or accident. Who cares which. The outcome is the same.

Once more unto the breach, I guess! I suppose that while Im here I should link to the two studies published last week and cited by Rose in her Substack to support her nonsensical claims that (1) the finding of a short nucleotide sequence in the spike protein mRNA sequence used in the Moderna vaccine is slam dunk evidence that SARS-CoV-2 was engineered and that the lab leak hypothesis for SARS-CoV-2 is true and (2) that SARS-CoV-2 permanently alters your DNA by being reverse transcribed and integrated into the DNA in its recipients chromosomes. Lets just say that neither Roses cited study from Lund University in Sweden about the supposed reverse transcription of the Pfizer/BioNTech mRNA-based vaccine into the DNA of human cells nor the study by Ambati et al about MSH3 homology support these hysterical claims.

Before I proceed, lets just reiterate that the idea that vaccines can permanently alter your DNA is not new to mRNA-based COVID-19 vaccines, although the nature of these vaccines makes that claim easier for antivaxxers to sell as plausible to those not familiar with molecular biology. Indeed, if you really look carefully at it, the claim that vaccines somehow changes your DNA actually dates back to before scientists even understood DNA as the basis of heredity, as illustrated, for example, by this famous Cow-Pock cartoon from 1802 by satirist James Gillray about smallpox vaccine:

Even a few years after Edward Jenner introduced the smallpox vaccine, the idea that vaccines somehow permanently alter humans had begun. (Source: Wikipedia and the Library of Congress, Prints & Photographs Division, LC-USZC4-3147, color film copy transparency.)

Savvy readers will notice how much a meme that was going around a year or so ago about the mRNA vaccines is very much of a piece with this 220-year-old cartoon:

How is this any different from 19th century antivax cartoons?

Similarly, the idea that an engineered virus, whether intentionally released or accidentally leaked from a laboratory, caused the pandemic is the same conspiracy theory that arises during every epidemic and pandemic, from various influenza pandemics to AIDS to Ebola. Of course, in the age of sophisticated molecular biology and genetics, antivaxxers can always find a special case that seems to show that the impossible is actually possible, and Jessica Rose is just continuing in this antivax tradition of misusing science, as Ill try to explain.

Before I discuss the two studies and the claims being made about them not just by Jessica Rose but by a number of antivaxxers, lets take a look at some basic biology and molecular biology, so that you understand why her claims are so beyond the ken. I realize that Ive done this before, but its been a while; so instead of just including links to my previous discussions, Ill include a brief explanation of something out of Biology 101, so that were all on the same page. If you know all of this, you can probably skip to the next section. If not, lets proceed.

mRNA vaccines rely on the central dogma of molecular biology. As Ive said many times before, Ive always hated the use of the word dogma associated with science, but no less a luminary than Francis Crick first stated it in 1958, and it has been restated over the years in various ways. Perhaps my favorite version of the central dogma was succinctly stated by Marshall Nirenberg in 1958 and has since been commonly paraphrased to say, DNA makes RNA makes protein, which about summed up all of molecular biology in five words. (Why I used the past tense in a moment.) In any event, for purposes of understanding the very basics of RNA vaccines, this is the main sequence that you need to understand.

Its true, of course, that DNA replicates from a DNA template and results in a double-stranded molecule that is very stable, as it has complementary sequences that tightly bind to each other in a sequence-specific fashion. This DNA template is unwound by enzymes that use the template to make RNA, which is single-stranded. That RNAwhen used to code for a protein called a messenger RNA or mRNAis then used by a ribosome to make protein out of amino acids. Again, to put it simply, each nucleotide equals one letter of the code; each three-nucleotide sequence (codon) equals one word that translates to an amino acid. Given that there are four nucleotides, there are 64 possible codons. Since there are only 20 amino acids, that means that most amino acids are encoded by more than one combination of nucleotides or more than one codon; i.e., the genetic code is redundant. Of course, as is the case with nearly everything in biology, its more complicated than that, as these diagrams show:

The Central Dogma of Molecular Biology. Information flows from DNA to RNA and then is used to make protein.

Information flows from DNA in the nucleus, to RNA, which is transported into the cytoplasm and used as a template to make protein.

There are more complications to this seemingly simple scheme, of course. mRNA doesnt always start out fully formed. Often its made as a longer precursor molecule, parts of which are spliced out by enzymes, to produce the final mRNA sequence before the mRNA molecule is used as a template to make protein. There are also other complexities that go beyond the central dogma, such as retroviruses, which make DNA using RNA templates, and microRNA, which can regulate gene expression by binding to specific sequences on mRNAs and blocking transcription and/or inducing the breakdown of the mRNA molecule, for instance. You dont really need to know the gory details of these processes or others, though, except retroviruses, whose ability to reverse the flow of information, so to speak, by transcribing DNA off of an RNA template using an enzyme known as reverse transcriptase will be very relevant to the discussion of the Swedish paper. HIV is the retrovirus that is the most well-known because of its ability to cause AIDS.

Exceptions aside, RNA vaccines consist mainly of, well, RNA. One problem with RNA vaccines is that RNA is an inherently unstable molecule. It is, after all, a messenger. It doesnt need to persist any longer than the message needs to be made. In aqueous solution, RNA molecules rapidly degrade. Indeed, the instability of RNA is why public health experts have been concerned about distributing RNA vaccines. Both Pfizer/BioNTech and Moderna adopted a similar strategy in designing their mRNA to encode the SARS-CoV-2 spike protein with stabilizing mutations added to lock this surface protein into a form easily recognizable to the immune system and therefore make it a better antigen. Pfizer and Moderna also used modified nucleosides (the RNA equivalent to DNA nucleotides) that are more stable to make their RNAs, and placed their RNA within a lipid nanoparticle (LNP) delivery system in which LNPs fuse with the cell membrane to deliver the RNA to the cytoplasm.

Naked mRNA of kind used in the Pfizer/BioNTech and Moderna vaccines rely on a very simple mechanism in which the LNPs deliver the mRNA for the SARS-CoV-2 spike protein to muscle cells, which then use the mRNA as a template to make spike, which is then displayed on the surface of the cell to be recognized by the immune system. Some of the vaccine does manage to get to the regional lymph nodes, where they incite an immune reaction as well. This is part of the reason why COVID-19 vaccines have been found to produce false positives in mammography done too soon after vaccination by causing temporary enlargement of the lymph nodes under the arm, which is why mammography recommendations have changed to incorporate waiting at least six weeks after receiving an intramuscular COVID-19 vaccine in the deltoid muscle before undergoing screening mammography.

Before I go on, let me emphasize that, even though SARS-CoV-2 is an RNA virus, it is not the same thing as a retrovirus and the mRNA in LNPs is not the same thing as RNA in retroviruses. Whereas SARS-CoV-2, like most RNA-based viruses, uses an enzyme called an RNA-dependent RNA polymerase (RdRp) to make copies of its RNA genome from an RNA template, retroviruses use an enzyme called reverse transcriptase to produce a DNA copy of their genetic information, which can then integrate into the human genome. Thats why, in order to produce a suitably fear-mongering narrative, antivaxxers usually have to look very hard for highly unusual, artificial, or special case experiments. Guess what? Rose found them.

So lets see what Jessica Rose wrote about these studies. Her message is, unsurprisingly, very much like that of antivaxxers 220 years ago:

I started to write this article yesterday but not one, but two papers of great interest to me have been published recently and require dissection and dissemination. They are entitled: MSH3 Homology and Potential Recombination Link to SARS-CoV-2 Furin Cleavage Site and Intracellular Reverse Transcription of Pfizer BioNTech COVID-19 mRNA Vaccine BNT162b2 In Vitro in Human Liver Cell Line, respectively.

Let me be clear here: These COVID-19 injectable products are perfect bioweapons either by design or accident. Who cares which. The outcome is the same.

Regarding the first paper, Rose writes:

Background for future: MSH3 (MutS Homolog 3) is gene that encodes a protein that is responsible for maintaining the stability of our genomes and suppressing tumor formation. This protein is DNA mismatch repair (MMR) protein which means that it recognizes and repairs bad base (nucleotide) insertions, deletions and mis-incorporations that come about inherently as part of DNA recombination and replication as well as DNA repair. You might have heard me talk about this in some of my presentations in reference to the recently-published paper describing 2 enzymes characterized to be inhibited by the spike protein.

we found that the spike protein localizes in the nucleus and inhibits DNA damage repair by impeding key DNA repair protein BRCA1 and 53BP1 recruitment to the damage site.

This more recent paper shows the presence of a 19 nucleotide-long sequence (19mer) that in fact, contains the sequence that encodes the furin-cleavage site of the SARS-nCoV-2 spike protein. In other fact, this 19mer has 100% sequence identity (100% query cover and matched identity anti-parallel complementarity 5-3) with patented sequences from as early as 2015. (I am checking on the link to MSH3.)

Aha! Theres the conspiracy theory! (More on that later.) First, though, Ill just note that this is far from the first time that Ive seen the claim that COVID-19 vaccines somehow interfere with DNA repair. Last time around, it was the claim that the vaccine somehow interferes with a process known as non-homologous end joining (NHEJ) and thereby make those receiving it much more susceptible to cancer. That claim was deceptive. Indeed, the study was very poor quality and had no biological relevance to human cancer risk, although it did contribute to the fascist antivax claim that vaccines somehow pollute the blood, making the unvaccinated purebloods. Unsurprisingly, its exactly the paper Rose cited.

As for the second study, Rose is no lessoff base:

Perhaps even more disturbing from a biological point of view, is something that many of us have hypothesized to be possible, has now been proven to be the case. Another new paper (link above) confirms that the Pfizer mRNA incorporates into human DNA. IN AS LITTLE AS 6 HOURS.

We detected high levels of BNT162b2 in Huh7 cells and changes in gene expression of long interspersed nuclear element-1 (LINE-1), which is an endogenous reverse transcriptase.

Huh is right.

Huh cells are immortal liver tumor cells and grow ad-infinitum if you give them love. They are good for using in assays that involve viral propagation. LINE-1 is a reverse transcriptase that we carry and comprises ~17% of our genome! LINE-1 retrotransposons are necessarily active during embryogenesis are aberrantly active in tumorigenesis.

This claim, as has often been the case, rests on a kind of experiment thats been done a number of times before to try to prove that the RNA virus SARS-CoV-2 can somehow mimic a retrovirus and insert its genetic sequence into the human genome, just like HIV. Thats why Ill discuss this study first.

Before I discuss this study, lets just reiterate that, for all the caveats and exceptions to the central dogma of molecular biology, for the vast majority of cases in normal mammalian cellular biology, information does not flow backwards from RNA to DNA. One of those exceptions, HIV and other retroviruses, requires two different enzymes to accomplish this backwards flow of genetic information. The first is the aforementioned reverse transcriptase, which reverse transcribes RNA sequences into DNA, destroying the RNA template in the process. However, that is not enough, as reverse transcriptase does not integrate the DNA strands thus produced into the human genome. A second enzyme is needed, a retroviral integrase. Integrases insert the double-stranded DNA produced by reverse transcriptase into the hosts chromosomal DNA; you can view this as a point of no return, after which the viral DNA becomes part of the host DNA, a form in which it is called a provirus, and a property of retroviruses that allow them to persist for so long in their hosts.

Retroviruses are not the only source of reverse transcriptase, as noted by Jessica Rose. Mammalian cells have very low levels of reverse transcriptase activity, so low that theyre usually not detectable under normal circumstances. One source is telomerase, which adds sequences known as telomere repeat sequences to the ends of chromosomes using an RNA template, to forestall the obligate chromosome shortening that occurs with each round of cellular replication. (Excessive telomerase activity is associated with the unlimited replicative potential of cancer.) Then there is LINE-1, mentioned by Rose and the focus of the paper.

LINE stands for long interspersed nuclear elements (LINEs). They are what are known as retrotransposons, also known as class 1 transposable elements or transposons via RNA intermediaries. Basically, retrotranposons can copy and paste themselves into different locations in the genome by making RNA and converting that RNA back into DNA through reverse transcription. Because its simple, Ill borrow an illustration of how they work from Wikipedia:

How retrotransposons copy and paste themselves into different locations in the genome.

You might reasonably be wondering at this point what LINE-1 could have to do with genetic sequences from the vaccine somehow getting into the human genome, thereby permanently altering your DNA. Youd be correct to wonder and likely would wonder even more if I told you that most LINEs in our genome are inactive and dont make any functional enzyme and that they greatly prefer their own RNA and dont randomly reverse transcribe just any old RNA. After all, retrotransposition (the process) requires that retrotransposons be able to replicate themselves and then paste the new copies elsewhere in the genome. It doesnt matter that, as Rose points out, LINE-1 does make up approximately 17% of the human genome. Very little of it is active in normal physiology, although increased LINE-1 is associated with cancer, neuropsychiatric disorders, and retinal diseases. (I almost hated to say that because it gives antivaxxers ideas.)

So what does the second study cited by Rose claim? What did the investigators do? First, lets look at the investigators rationale:

A recent study showed that SARS-CoV-2 RNAs can be reverse-transcribed and integrated into the genome of human cells [25]. This gives rise to the question of if this may also occur with BNT162b2, which encodes partial SARS-CoV-2 RNA. In pharmacokinetics data provided by Pfizer to European Medicines Agency (EMA), BNT162b2 biodistribution was studied in mice and rats by intra-muscular injection with radiolabeled LNP and luciferase modRNA. Radioactivity was detected in most tissues from the first time point (0.25 h), and results showed that the injection site and the liver were the major sites of distribution, with maximum concentrations observed at 848 h post-dose [26]. Furthermore, in animals that received the BNT162b2 injection, reversible hepatic effects were observed, including enlarged liver, vacuolation, increased gamma glutamyl transferase (GT) levels, and increased levels of aspartate transaminase (AST) and alkaline phosphatase (ALP) [26]. Transient hepatic effects induced by LNP delivery systems have been reported previously [27,28,29,30], nevertheless, it has also been shown that the empty LNP without modRNA alone does not introduce any significant liver injury [27]. Therefore, in this study, we aim to examine the effect of BNT162b2 on a human liver cell line in vitro and investigate if BNT162b2 can be reverse transcribed into DNA through endogenous mechanisms.

This is thin gruel as a rationale. I note that Ive discussed the cited study before, which involved the intravenous injection of a large amount of LNPs with a different mRNA than the vaccines spike protein mRNA, again an artificial design intended to make determination of the biodistribution of the LNPs possible given that in an intramuscular injection the vast majority of the mRNA remained at the injection site and in nearby lymph nodes.

I also note that it is not a new claim that SARS-CoV-2 itself is reverse transcribed in the infected cell to integrate with the host genome. This is a study from last summer that antivaxxers previously used to claim that, based on the supposed ability of SARS-CoV-2 to reverse transcribe, the vaccine could do the same. Lets just say that this study was justifiably harshly criticized as not reproducible, very rare, and almost certainly artifacts of the experimental conditions used, given that appropriate controls werent used. To cite Ed Nirenberg again, no, SARS-CoV-2 is not reverse-transcribed to any significant extent, the publication of the study in PNAS notwithstanding.

I get the same vibes from this new study. So what did the authors do? They did indeed take Huh7 liver cells and expose them to the Pfizer/BioNTech vaccine (BNT162b2), at 200,000 cells/well in 24-well plates. Then they did this:

BNT162b2 suspension was then added in cell culture media to reach final concentrations of 0.5, 1.0, or 2.0 g/mL. Huh7 cells were incubated with or without BNT162b2 for 6, 24, and 48 h. Cells were washed thoroughly with PBS and harvested by trypsinization and stored in 80 C until further use.

After 48 hours, the cells were harvested. RNA was extracted for PCR, and in other experiments genomic DNA was extracted from the cells. Of particular importance however, is that the segment of the nucleic acid for the spike protein that was amplified by PCR was this:

Spike amplicon, specifically the part of the sequence amplified by PCR in this experiment.

Why did they pick primers that amplified only this segment of the gene for spike protein? PCR efficiency drops off the longer the segment that is amplified, and a 444 base segment is actually rather long for quantitative real time PCR. In any event, this choice means that the only thing that can be said is that perhaps this segment of spike was reverse transcribed. Another thing to note is that a very high concentration of vaccine was used, microgram quantities for only 200,000 cells. That in and of itself is very artificial, but thats not all thats artificial. As Ed Nirenberg points out, Huh7 was derived from a liver cancer. Unsurprisingly, the Huh7 genome is, as is the case with many cancer-derived cell lines, really messed up.

He also notes that L-1 expression is substantially overexpressed in cancer (i.e., cancer cells have a lot more of it than normal cells).

In other words, the investigators stacked the deck by using a cell line that has a high level of LINE-1. If I were a peer reviewer for this study, I would have demanded that the investigators use a more genomically normal cell line. No cell line that is immortalcan propagate indefinitelyhas a normal genome, but some have genomes that are less messed up than others. There are a number of respiratory cell lines, for instance, that could work, or what about simple primary cultures of vascular endothelial cells, such as HUVECs (human umbilical vein endothelial cells)? Why did they use only one cell line? In general, if you see a paper that uses only one cell line, be very, very skeptical, not just for COVID-19 but for any basic science studies.

So back to the paper. What did the authors find? Yes, they found that the vaccine, as expected, drove spike mRNA expression, leading to high levels in the cells, while not having much effect on LINE-1 expression, concluding that increased LINE-1 expression compared to control was observed at 6 h by 2.0 g/mL BNT162b2, while lower BNT162b2 concentrations decreased LINE-1 expression at all time points. If you look at the figure, I call noise, because it doesnt make a lot of physiologic sense that the lower vaccine concentrations would depress LINE-1 expression but lead to increased expression only at the 6 hour time point.

Whenever you see a graph like this, get out your BS detector.

Hilariously, this chart is the very same one included in Roses article, but she fails to see its shortcoming. Amusingly, the authors used two-tailed Students t-tests to compare these differences, which is not the correct statistical test for multiple time-dependent comparisons, and the finding of this result is most consistent with noise. Had I been a peer reviewer, I would definitely have called out the statistics used.

But what about reverse-transcribed DNA for spike? Yes, the authors did detect that in the genomic DNA isolated from the cells. They even sequenced the amplified segment and found that it was the same spike sequence targeted by the PCR primers. Checkmate, scientists! Not quite, and the authors even add some weasel words:

In this study we present evidence that COVID-19 mRNA vaccine BNT162b2 is able to enter the human liver cell line Huh7 in vitro. BNT162b2 mRNA is reverse transcribed intracellularly into DNA as fast as 6 h after BNT162b2 exposure. A possible mechanism for reverse transcription is through endogenous reverse transcriptase LINE-1, and the nucleus protein distribution of LINE-1 is elevated by BNT162b2.

Note that this study most definitely did not show that this reverse transcription had anything to do with LINE-1, leaving the authors to speculate. They could have presented evidence that LINE-1 was responsible, perhaps by knocking it out to produce cells that dont make it or using siRNA that targets the LINE-1 mRNA to decrease its level, and showing that that it blocked the reverse transcription of spike. They didnt do that. So they speculate, and antivaxxers ignore that this is speculation to present it as a fact that SARS-CoV-2 is reverse transcribed through the reverse transcriptase activity of LINE-1.

Next:

Our study shows that BNT162b2 can be reverse transcribed to DNA in liver cell line Huh7, and this may give rise to the concern if BNT162b2-derived DNA may be integrated into the host genome and affect the integrity of genomic DNA, which may potentially mediate genotoxic side effects. At this stage, we do not know if DNA reverse transcribed from BNT162b2 is integrated into the cell genome. Further studies are needed to demonstrate the effect of BNT162b2 on genomic integrity, including whole genome sequencing of cells exposed to BNT162b2, as well as tissues from human subjects who received BNT162b2 vaccination.

This led to some epic handwaving:

The cell model that we used in this study is a carcinoma cell line, with active DNA replication which differs from non-dividing somatic cells. It has also been shown that Huh7 cells display significant different gene and protein expression including upregulated proteins involved in RNA metabolism [56]. However, cell proliferation is also active in several human tissues such as the bone marrow or basal layers of epithelia as well as during embryogenesis, and it is therefore necessary to examine the effect of BNT162b2 on genomic integrity under such conditions. Furthermore, effective retrotransposition of LINE-1 has also been reported in non-dividing and terminally differentiated cells, such as human neurons [57,58].

Sure thing, guys, but no. This is, as I said, just handwaving.

As Ed Nirenberg asks, why didnt they bother to do the necessary follow-up experiments to determine if this DNA sequence is actually integrated into the genome? Come to think of it, why didnt they do PCR of the entire spike sequence to show that the full length sequence had been reverse-transcribed? Or even just do PCR of different fragments from the spike sequence? It boggles the mind.

None of this stops Rose from going straight off the end of the plank of science to this conclusion:

LINE-1 retrotransposons are also involved during early embryonic development. Since LINE-1 expression levels are significantly increased then what effect is this over-expression having on embryogenesis?

We found that too much or too little LINE-1 expression caused development to come to a halt. This means that the precise timing and level of retrotransposon expression is critical for the development of the embryo.

I need a walk. This article will be updated.

I can hardly wait for Roses updates, given how far she had to reach to find some rationale to take a highly artificial experiment that almost certainly doesnt show that the mRNA for the SARS-CoV-2 spike used in COVID-19 vaccines is reverse transcribed under normal conditions, much less integrated into the genome of the cells in which it finds itself. Im guessing that her updates will be as hilariously off base as her original post.

But what about the first study?

The second paper cited by Rose turns out to be all about the lab leak conspiracy theories. Its not about the more plausible variant of the lab leak concept (but still highly unlikely compared to a natural origin) in which a naturally occurring bat coronavirus somehow escaped the virology lab at Wuhan, thereby starting the pandemic, but rather the utter bonkers idea that SARS-CoV-2 is an engineered coronavirus that escaped the laboratory, thanks to gain of function research. Of course this version is a different twist on the same idea, specifically that the finding of a short DNA sequence from a larger sequence patented by Moderna years ago as part of its cancer research effort in the sequence in the spike protein mRNA used in the Moderna vaccine is slam-dunk evidence for the lab leak hypothesis. Lets just say that its not.

The article is a perspective article, which means its basically the peer-reviewed scientific equivalent of an op-ed article. I also cant help but wonder how the authors got something like this published on the basis of doing some BLAST searches of the Genbank database, something basically anyone with an Internet connection can do to see if nucleotide and protein sequences exist in all the ones reported to the database. I used to do BLAST searches all the time, and have even done a few going way, way back to the beginning of the pandemic, when James Lyons-Weiler tried to prove that there were sequences from a common plasmid in SARS-CoV-2, thus demonstrating that it was engineered. (Hint: He failed.)

The op-ed asserts:

A peculiar feature of the nucleotide sequence encoding the PRRA furin cleavage site in the SARS-CoV-2 S protein is its two consecutive CGG codons. This arginine codon is rare in coronaviruses: relative synonymous codon usage (RSCU) of CGG in pangolin CoV is 0, in bat CoV 0.08, in SARS-CoV 0.19, in MERS-CoV 0.25, and in SARS-CoV-2 0.299 (9).

A BLAST search for the 12-nucleotide insertion led us to a 100% reverse match in a proprietary sequence (SEQ ID11652, nt 2751-2733) found in the US patent 9,587,003 filed on Feb. 4, 2016 (10) (Figure 1). Examination of SEQ ID11652 revealed that the match extends beyond the 12-nucleotide insertion to a 19-nucleotide sequence: 5-CTACGTGCCCGCCGAGGAG-3 (nt 2733-2751 of SEQ ID11652), such that the resulting mRNA would have 3- GAUGCACGGGCGGCUCCUC-5, or equivalently 5- CU CCU CGG CGG GCA CGU AG-3 (nucleotides 23547-23565 in the SARS-CoV-2 genome, in which the four bold codons yield PRRA, amino acids 681684 of its spike protein). This is very rare in the NCBI BLAST database.

The correlation between this SARS-CoV-2 sequence and the reverse complement of a proprietary mRNA sequence is of uncertain origin. Conventional biostatistical analysis indicates that the probability of this sequence randomly being present in a 30,000-nucleotide viral genome is 3.21 1011 (Figure 2).

Wow. That sounds damning, doesnt it?

Of course, those following various lab leak hypotheses for the origin of SARs-CoV-2 will immediately recognize the reference to the furin cleavage site. An interesting feature of the SARS-CoV-2 spike protein is that it consists of two subunits and, between those two subunits, S1 and S2, sits a site where a human protein called furin cleaves the protein, resulting in the two functional subunits. In fact, you might even recognize the claim that the two successive CGG codons, coding for two arginine residues in the furin cleavage site, is a rare codon usage. Lets just say that, in terms of the pandemic, this is a hoary old bit of SARS-CoV-2 conspiracy mongering dating back to very early in the pandemic and popularized by science writer-turned-COVID-19-conspiracy theorist Nicholas Wade. Moreover, the term randomly present in a 30 kb viral genome is doing a lot of heavy lifting, mainly because no one is saying that its random. Do the authors think that beta coronaviruses (of which SARS-CoV-2 is one) are made up of random sequences unrelated to each other? Of course not! Theyre highly related.

Indeed, it has been pointed out just how off-base the probability argument is:

Lawrence Young, Ph.D., a virologist at the University of Warwick, said it was interesting but probably not significant enough to suggest the virus was manipulated in a laboratory. Were talking about a very, very, very small piece made up of 19 nucleotides. So it doesnt mean very much to be frank, if you do these types of searches you can always find matches. Sometimes these things happen fortuitously, sometimes its the result of convergent evolution (when organisms evolve independently to have similar traits to adapt to their environment). Its a quirky observation but I wouldnt call it a smoking gun because its too small. It doesnt get us any further with the debate about whether COVID was engineered.

Simon Clarke, Ph.D., a microbiologist at Reading University, also questioned the one-in-three trillion statistics, saying, There can only be a certain number of [genetic combinations within] furin cleavage sites. They function like a lock and key in the cell, and the two only fit together in a limited number of combinations. So its an interesting coincidence but this is surely entirely coincidental.

If youre a conspiracy theorist, of course, there is no such thing as a coincidence, at least if its about something you want to believe to be true. In any event, this is exactly correct. The wrong argument to make is how common such a 19 nucleotide sequence would occur randomly in a viral genome. You have to take into account function, which greatly constrains the sequences one can find, plus how short this sequence is, which makes it very much more likely that it did indeed occur by chance.

As Ive discussed before, it turns out that a CGGCGG sequence is not all that uncommon. It has been found in other coronaviruses, for example, some isolates of MERS coronavirus. Furin cleavage sites are also found in a number of other coronaviruses, as discussed in this recent review article. Although uncommon, furin cleavage sites are not so uncommon in coronaviruses as to be any sort of strong evidence of laboratory manipulation. Moreover, there are known natural mechanisms by which such a sequence could have arisen, as has been discussed extensively on Twitter and elsewhere. But what about that 19-nucleotide sequence?

I will note, however, that the claim made in this op-ed is a rather interesting spin on the same old claims about the SARS-CoV-2 furin cleavage site in that I havent seen it before. In this case, the authors are claiming that this 19 nucleotide sequence found in MSH3, a DNA repair gene, is the very same sequence patented by Moderna seven years ago and found in the furin cleavage site of the spike sequence used in the Moderna vaccine, with the implication that SARS-CoV-2 was engineered:

The proprietary sequence SEQ ID11652, read in the forward direction, encodes a 100% amino acid match to the human mut S homolog 3 (MSH3) (9). MSH3 is a DNA mismatch repair protein (part of the MutS beta complex) (11). SEQ ID11652 is transcribed to a MSH3 mRNA that appears to be codon optimized for humans (12). We did not find the 19-nucleotide sequence CTCCTCGGCGGGCACGTAG in any eukaryotic or viral genomes except SARS-CoV-2 with 100% coverage and identity in the BLAST database (Supplementary Tables 13).

A claim that the authors make explicit:

The absence of CTCCTCGGCGGGCACGTAG from any eukaryotic or viral genome in the BLAST database makes recombination in an intermediate host an unlikely explanation for its presence in SARS-CoV-2.

Ergo, this sequence must have been engineered. Add to that the Moderna patent and checkmate, right? Not so much. For one thing, this sequence is the reverse complement of the sequence found on the furin cleavage site. What does that mean? Its on the opposite strand, the strand that doesnt code for protein. The authors do a lot of handwaving to try to explain this, mainly by claiming that cells co-transfected with a SARS-like virus expressing RdRp could attach to this 19-nucleotide sequence (15) and permit integration of a fragment from the negative strand into the viral genome, including the FCS, despite being on the opposite strand of the open reading frame, RdRp being the RNAse-dependent RNA polymerase mentioned early in this post. Perhaps, but this comes across to me more as an attempt to wave away the very substantive criticism that a sequence that isnt the strand that codes for the actual protein.

Just for yucks, I did some BLAST searches myself, and after doing a number of them I concluded that this result was not easy to come by. I had to search the sequence patented by Moderna versus SARS-CoV-2 with the loosest parameters that allowed for the least degree of similarity; otherwise there were zero matches, largely because stricter parameters only find longer stretches of sequence similarity. Thats why I now rather suspect that the investigators searched the sequence for SARS-CoV-2 versus every sequence ever patented by Moderna, and the best they could come up with was this short 19 amino acid match, after which, even though it was the reverse complement and not even on the strand that codes for the protein, started searching other Moderna patents for the same 19mer and found a few more hits.

Making me even surer that this is random is Roses own further observations:

Most disturbing, however, is that HZ246785.1 was patented 7 years ago by MODERNA THERAPEUTICS (2015) and more recently by ModernaTX Inc (2017/2018). Other patents for this same 19mer were filed by CAMBIA (2015) and CureVac AG (2021). A shorter version with 89% query and 100% matched identity were found in patents filed by Monsanto Technology LLC (2016) and Metanomics GmbH (2015). Just noting some familiar names here. Not making any claims.

Then, thankfully, bioinformatician Moreno Colaiacovo provided a lengthy explanation dating back to December why theres nothing to see here; so Ill cite his brief discussion in its entirety:

When challenged, Colaiacovo noted:

And:

Think of it this way. Whoever initially found this 19 nucleotide sequence did a lot of work to find it. Yet, this is the best they could come up with as slam dunk evidence that SARS-CoV-2 was engineered by Moderna, to the point where they have to do serious contortions make such a short stretch seem nefarious? Another way to think of it is just how unlikely it is that this shared 19-mer is proof of some sort of engineering or that Moderna knew about SARS in 2016. Again think of how unlikely the implied necessary scenario would be: Somehow during an experiment cells transfected with the sequence in the patent were infected by a SARS-like virus, and then there was a recombination event that led to SARS-CoV-2 with a furin cleavage site containing that sequenceand not even on its coding strand, but on its reverse complement strand! This is reaching homeopathy-levels of implausibility.

As I like to say, in antivaxland, everything old is new again in the age of COVID-19. However, as the pandemic grinds on, entering its third year, even everything old that was new again when COVID-19 struck is becoming old. The idea that COVID-19 vaccines permanently alter your DNA has now spawned a number ofif youll excuse my use of the termvariants. So has the version of the lab leak hypothesis that asserts that SARS-CoV-2 was somehow engineered, this variant adding a conspiracy theory that implies that one of the manufacturers of the first successful COVID-19 vaccines must have somehow known the sequence of SARS-CoV-2 nearly four years before the pandemic. What Jessica Rose is promoting, aided and abetted by these awful studies published in bottom feeding journals, is simply helping to spread variants of these two conspiracy theories.

More:
The return of the revenge of COVID-19 mRNA vaccines permanently alter your DNA and lab leak - Science Based Medicine