Category Archives: Transhuman News

About 1 in 44 children in the U.S. are diagnosed with autism spectrum disorder (ASD) by the age of 8, according to the 2018Centers for Disease Control and Prevention surveillance. How a childs DNA contributes to the development of ASD has been more of a mystery. Recently, clinicians and scientists have looked more closely at new, or de novo, DNA changes, meaning they only are present in affected individuals but not in the parents. Researchers have seen that these changes could be responsible for about 30% of ASD. However, which de novo variants play a role in causing ASD remains unknown.

Researchers at Baylor College of Medicine and Texas Childrens Hospital have taken a new approach to looking at de novo ASD genetic variants. In this multi-institutional study published in the journalCell Reports, they applied sophisticated genetic strategies in laboratory fruit flies to determine the functional consequences of de novo variants identified in theSimons Simplex Collection (SSC), which includes approximately 2,600 families affected by autism spectrum disorder. Surprisingly, their work also allowed them to uncover a new form of rare disease due to a gene called GLRA2.

ASDs include complex neurodevelopmental conditions with impairments in social interaction, communication and restricted interests or repetitive behaviors. In the current study, we initiated our work based on information from a cohort of ASD patients in the SSC whose genomes and those of their families had been sequenced, said co-corresponding authorDr. Shinya Yamamoto, assistant professor ofmolecular and human geneticsandof neuroscienceat Baylor and investigator at theJan and Dan Duncan Neurological Research Instituteat Texas Childrens. Our first goal was to identify gene variants associated with ASD that had a detrimental effect.

The team worked with thefruit fly lab modelto determine the biological consequences of the ASDassociated variants. They selected 79 ASD variants in 74 genes identified in the SSC and studied the effect of each ASDlinked gene variant compared to the commonly found gene sequence (reference) as a control, from three different perspectives.

Co-first author,Dr. Paul Marcogliese,postdoctoral fellow in Dr. Hugo Bellens lab, coordinated the effort on knocking out the corresponding fly gene, and examining their biological functions and expression patterns within the nervous system. They then replaced the fly gene with the human gene variant identified in patients, or the reference sequence, and determined how it affected biological functions in the flies.

Working with fruit flies carrying either the reference human gene or the variant forms, co-first authorDr. Jonathan Andrews, postdoctoral fellow inDr. Michael Wanglers lab at Baylor, was the point person investigating how these gene variants affected fly behavior. As ASD patients exhibit patterns of repetitive behavior as well as changes in social interaction, he evaluated the effect of the patient variants on an array of social and non-social fly behaviors, such as courtship and grooming. Its interesting to see that manipulation of many of these genes also can cause behavioral changes in the flies, Andrews said. We found a number of human genes with ASD variants that altered behavior when expressed in flies, providing functional evidence that these have functional consequences.

The third approach involved overexpressing the genes of interest in different tissue types in fruit flies. Co-first authorsSamantha Dealand Michael Harnish, two graduate students in Baylors Graduate Programs inDevelopmental BiologyandGenetics and Genomics, respectively, working in Dr. Yamamotos lab, headed these studies. While some gene variants may lead to conditions because they produce defective proteins, others may lead to disease because they cause overabundance or aberrant function of a particular protein, which can disrupt biological processes. We investigated whether overexpressing gene variants found in individuals with ASD might explain the detrimental effect for some of these genes, Deal said.

Altogether, the team generated more than 300 fly strains in which they conducted functional studies of human gene variants associated with ASD. Their screen elucidated 30 ASD-linked variants with functional differences compared to the reference gene, which was about 40% of the genes for which they were able to perform a comparative functional assay.

Some of the variants we studied had functional consequences that were moderately or clearly predicted to be disruptive, but other variants were a surprise. Even the state-of-the-art computational programs couldnt predict they would have detrimental effects, said Yamamoto. This highlights the value of using multiple, complementary approaches to evaluate the functional consequences of genetic variants associated with ASD or other conditions in a living animal. Our fruit fly approach is a valuable tool to investigate the biological relevance of gene variants associated with disease.

In addition, the wealth of data generated by the researchers revealed gene variants not previously connected with other neurodevelopmental diseases and uncovered new aspects of the complexity of genetic diseases.

GLRA2 was one gene we specifically focused on to follow up,Dr. Ronit Marom, assistant professor of molecular and human genetics at Baylor and lead clinician of this work said. We identified 13 patients, five males and eight females, carrying rare variants of this X-linked gene that had not been established as a neurological disease gene before. Furthermore, males and females carried variants with different types of functional consequences and the spectrum of neurological characteristics among these 13 patients was different between the two groups. For instance, many of the boys carried loss of function variants and had ASD, while the girls did not. They mainly presented with developmental delay as the main characteristic of their condition, and carried gain of function variants.

The picture that emerges is that ASD may not be one disorder involving many genes. It may actually be hundreds of genetic disorders, like those caused by certain GLRA2 variants, said Wangler, assistant professor of molecular and human genetics at Baylor and co-corresponding author of the work. We think that this information is important to physicians seeing patients with ASD.

For a complete list of the contributors to this work, their affiliations and the financial support for this project, seethe publication.

See the original post here:
Fruit fly study uncovers functional significance of gene mutations associated with autism - Baylor College of Medicine News

A Yale Cancer Center research team has identified novel oncogenic gene fusions in lung and pancreatic cancer, as well as sarcoma. The fusions involve RASGRF1 (an activator of RAS signaling) and promote cellular changes leading to tumor development. The research is described online ahead of print in Clinical Cancer Research.

The research team studied 103 lung adenocarcinomas in the Yale Lung Cancer Biorepository collected from individuals with minimal smoking history to assess the frequency of known oncogenic mutations in these tumors and to identify potential new oncogenic alterations. The team performed whole-exome sequencing and RNA sequencing on a subset of these tumors at the Yale Center for Genome Analysis and identified an established oncogenic mutation in 98 of the 103 tumors.

Through further analysis of one of the tumors that lacked a known oncogenic alteration, they found a novel gene rearrangement causing a fusion between two genes called OCLN and RASGRF1.

Using public databases of sequenced human cancer cell lines and tumors, the team identified two similar RASGRF1 fusions in pancreatic cancer and in sarcoma and demonstrated that these three fusions turn on RAS signaling and have tumor-promoting properties in cells. The research findings were established in part with mouse models through a collaboration with the Yale Center for Precision Cancer Modeling. From a small molecule inhibitor screen performed at the Yale Center for Molecular Discovery, the research team determined that cells containing RASGRF1 fusions are sensitive to trametinib, a targeted therapy that blocks a pathway activated by RAS signaling.

Through the collaborative efforts of several Yale Cancer Center Shared Resources, we characterized a new class of oncogenic fusions. While these fusions are uncommon, they occur in several types of cancer and our findings suggest a potential treatment strategy for advanced tumors with these fusions, said Frederick Wilson, MD, PhD, Assistant Professor of Medicine (Medical Oncology) and senior author of the paper.

Funding for the study was provided by the Doris Duke Charitable Foundation, the National Institutes of Health, the Beatrice Kleinberg Neuwirth Fund at Yale Cancer Center, and the Robert M. Harris Fund for Lung Cancer Research at Yale Cancer Center. The Yale Lung Cancer Biorepository is supported by the Yale SPORE in Lung Cancer.

Additionally, the following Yale authors contributed to this study: Lisa Hunihan, Dejian Zhao, Heather Lazowski, Man Li, Yuping Qian, Laura Abriola, Yulia V. Surovtseva, Viswanathan Muthusamy, Lynn T. Tanoue, Bonnie E. Gould Rothberg, Kurt A. Schalper, and Roy S. Herbst.

See the rest here:
New Class of Oncogenic Fusions Revealed in Lung and Pancreatic Cancer - Yale School of Medicine

The genetic factors that give sufferers of endometriosis a higher risk of ovarian cancer have been explained, and the connection could increase the chances of finding treatments for both.

Endometriosis where tissue similar to the lining of the womb grows outside the uterus is among the most under-diagnosed diseases in countries where healthcare is sufficient to identify other common conditions. On average, it takes women suffering from it seven years to get diagnosed, because so many doctors dismiss descriptions of horrifying period pain, nausea, and other symptoms produced when the cells respond to hormones as if they were where they should be. Indeed, it's apparently easier to get funding to study whether having endometriosis makes women more attractive to men than for research to treat its effects.

This neglect may not only leave women to suffer intense pelvic pain and potential infertility, but it could also risk their lives following evidence those with endometriosis also carry a slightly heightened risk of epithelial ovarian cancer. However, a new paper in Cell Reports Medicine offers hope that the link could be turned to the advantage of sufferers of both conditions.

Although rarely directly fatal, the paper notes endometriosis shares features with cancer, including metastatic-like behavior, tissue invasion, proliferation, angiogenesis [formation of blood vessels], and decreased apoptosis [normal cell death].

The authors studied the genomes of 25,000 sufferers of ovarian cancer and 15,000 people with endometriosis. Such large sample sizes allowed them to look for features unusually common in both groups.

Our research shows that individuals carrying certain genetic markers that predispose them to having endometriosis also have a higher risk of certain epithelial ovarian cancer subtypes, namely clear cell and endometrioid ovarian cancer, lead author Dr Sally Mortlock of the University of Queensland said in a statement.

Rather than a single common gene, the authors found 28 locations within the human genome associated with both conditions, with a shared underlying signal at 19 of them. Identification of those genes offers a set of targets for researchers to work on, either through gene therapy or by identifying the proteins the genes code for.

For the one in nine women with endometriosis, knowing they are also at extra risk of ovarian cancer could add anxiety to everything else they are going through. However, Mortlock notes the extra danger only applies to certain forms of ovarian cancer clear cell and endometrioid and consequently the extra risk is small.

Overall, studies have estimated that 1 in 76 women are at risk of developing ovarian cancer in their lifetime and having endometriosis increases this slightly to 1 in 55, so the overall risk is still very low, Mortlock said. A very weak correlation was also found with high-grade serous ovarian cancer.

The findings, therefore, could be more important for the research implications than what they say about an individual's personal danger.

Nevertheless, if the message of the connection to cancer sinks in, this might be one way to get more doctors to take patients seriously when they describe endometriosis symptoms, which would be significant indeed.

Continue reading here:
Genetic Connection Between Endometriosis and Ovarian Cancer Identified - IFLScience

New research underscores the value of sharing genomic information to advance gene matching for diagnosis and discovery

GAITHERSBURG, Md., March 16, 2022 /PRNewswire/ -- GeneDx, Inc., a leader in genomic analysis, today announced newly published research demonstrating the value of data sharing and research participation on a platform that supports clinician connections to rapidly uncover new gene-disease relationships, an approach which has resulted in publication of more than 200 new associations.

The research, published in Human Mutation, details the results of GeneDx's contributions to GeneMatcher, a genomic database designed to enable connections between clinicians and researchers. Despite the rapid advances of genetic medicine in the last 15 years, expanding knowledge about the connections between genetic variation and human health remains a critical need. Through GeneDx's contributions, at least 200 new associations have been published in the past three years, reporting either new disease-gene relationships or expanded clinical information for known disease-causing genes. A systematic approach that includes identifying candidate genes observed at the company's laboratory, helping support clinician-led research and following through to publication has yielded an important platform for expanding understanding of the links between genes and health.

Further, participation in GeneMatcher has helped patients and their families find answers that otherwise may not have been possible, by connecting them with researchers and confirming disease-gene relationships. For patients facing rare diseases, resolving uncertain findings or identifying new relationships that can confirm a diagnosis may mean the difference between years of testing and receiving an accurate diagnosis.

"We often talk about the importance of genomic information for establishing a diagnosis and unlocking access to precision therapies for individual patients. Our experience with GeneMatcher shows that is just the first step in the value testing creates. Patients and clinicians who participate in research pay it forward by spurring new discoveries," said Paul Kruszka, M.D., chief medical officer at GeneDx. "With thousands of rare diseases impacting millions of patients, establishing an effective approach to speed up the identification of disease-gene relationships and putting that knowledge to work to help patients is critical."

GeneDx's database of more than 300,000 clinical exomes has been a major driver of discovery. This dataset, supported by carefully annotated and structured clinical information, powers a potent diagnosis and discovery engine. Today roughly one-quarter of the clinically actionable findings provided to patients come from discoveries first made at GeneDx.

About GeneDx

GeneDx, Inc. is a global leader in genomics, providing testing to patients and their families worldwide. Originally founded by scientists from the National Institutes of Health, GeneDx offers a world-renowned clinical genomics program with particular expertise in rare and ultra-rare genetic disorders. In addition to its market-leading exome sequencing service, GeneDx offers a suite of additional genetic testing services, including diagnostic testing for hereditary cancers, cardiac, mitochondrial, neurological disorders, prenatal diagnostics, and targeted variant testing. GeneDx is a subsidiary of BioReference Laboratories, Inc., a wholly owned subsidiary of OPKO Health, Inc. (NASDAQ: OPK). To learn more, please visit http://www.genedx.com.

CONTACT: Julie McKeough, [emailprotected]

SOURCE GeneDx, Inc.

Here is the original post:
GeneDx Announces Discovery of 200 New and Expanded Genetic Conditions - PR Newswire

The etiology of acne is complex and multifactorial with genetics playing a large role in determining risk, particularly for those individuals with severe acne. The results of a recent study have further elucidated the genetics of acne and advanced the knowledge of the genetic basis of acne risk by identifying versions of the genes that are common among individuals who suffer from this very common inflammatory skin disorder.

It is estimated that more than 85% of teenagers are affected by acne to some degree, and up to 8% have been reported with severe disease, making acne the most prevalent skin disease worldwide. Depending on the severity of the disease, acne can significantly impact self-image and the quality of life (QOL). Major complications of acne include scarring as well as the, at times, significant psychosocial distress that can persist long after active lesions have disappeared.

Approximately 80% of a persons risk of suffering from severe acne can be explained by differences in their genetic makeup, said Miguel E. Rentera, PhD, senior research fellow, Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia, and co-author of the study. It is not a single gene but rather variations across hundreds of genes in the genome that determine whether someone is likely to get acne or not, and the extent or severity of the condition.

Rentera and fellow colleagues recently performed a large meta-analysis of genome-wide association studies (GWAS) of acne undertaken in 9 independent cohorts compromising a total of 615,396 study participants. Of the participants, 20,165 were acne cases and 595,231 were controls, making it the largest study of its kind, with the aim of identifying specific genetic variants that are more common among people with moderate or severe acne relative to those who have mild or no acne. Fine-mapping and genome-wide analytical approaches were combined to gain insights into the underlying genes and pathways through which the associated loci contribute to disease susceptibility.

Researchers could identify 29 new genetic variants that are more common in individuals with acne, as well as confirm 14 of the 17 variants already known to be associated with the condition, raising the total number of known acne risk loci to 46. Results also exposed relationships between acne and other complex/common traits, including behavioral, hormonal, inflammatory, and psychiatric traits, as well as shared molecular basis between acne and Mendelian hair and skin disorders, including pustular psoriasis.

Fifteen of these loci have been reported to have an effect in European populations while the remaining 2 have been reported to have an effect in a Han Chinese population. This highlights the potential differences in the genetic architecture of acne between different ethnic populations, warranting further investigation in studies of diverse ancestry. According to Rentera, however, one of the main limitations is the lack of availability of cohorts or biobanks focused on diverse ancestries.

Our study results highlight possible molecular pathways that are implicated in acne, opening new avenues for fundamental research and development of therapeutic targets, Rentera said. Looking forward, we could apply this knowledge to do genetic tests of acne risk and identify those individuals who are likely to present with acne.

Novel research studies will need to be designed and performed to better understand the role of the newly identified acne genes and the mechanisms of action of these new variants need to be characterized and their potential as therapeutic targets to treat acne need to be assessed, he said.

According to Rentera, the estimation of individual genetic acne risk scores relative to the general population will be perhaps the most immediate application of the current study findings.

We demonstrated that it is possible to use a persons genetic information to estimate their genetic risk of developing acne based purely on which genetic variants they inherited from their parents, Rentera said. In the future, we will be able to identify those individuals who are at high-risk of acne many years before they even notice the first signs.

Finding genes implicated in acne is the first step toward patient stratification and personalized medicine. Although continued research has been inching closer towards personalized medicine on the genetic level, this fulfillment is likely a few years away. A clinicians treatment and management choices in the future could be informed by the genetic profile of each individual patient, Rentera said, however there is still much work to be done regarding characterizing the genetic basis of different acne types and treatment response across different life stages.

This research enables a much better understanding of the genetic basis of acne, and investigation of these variants further illustrates the shared biology processes with other skin and hair traits as well as a shared genetic etiology with other common diseases, Rentera said. However, identifying the relevant genes is not the end but rather the beginning of a journey of discovery.

This article was originally published by sister publication Dermatology Times.

Reference

Mitchell BL, Saklatvala JR, Dand N, et al.Genome-wide association meta-analysis identifies 29 new acne susceptibility loci.NatCommun. 2022 Feb 7;13(1):702. doi: 10.1038/s41467-022-28252-5.

Originally posted here:
Examining the genetics of acne - Contemporary Pediatrics

According to Alethea Gerding, Managing Editor, ASCPT, "The article has been downloaded more than 3,000 times"

These results have important clinical implications as more than 4.2 million people in the US are known to suffer from painful DPN and nearly 1.3 million patients are considered to be refractory, meaning currently available medications do not work for them (Painful Diabetic Neuropathy, GlobalData 2018).

Helixmith launched a second phase 3 trial for DPN, REGAiN-1A (VMDN-003-2), in the US and are targeting release of top line results by the end of 2022. The company is planning to start a third phase 3 for DPN in the second half of 2022.

Key points of the CTS paper

About Diabetic Peripheral Neuropathy

Painful DPN is a common and debilitating complication of diabetes mellitus that has a profound negative impact on quality of life, sleep, and mood. Current therapies are palliative and do not target the mechanisms underlying painful DPN. Moreover, symptomatic relief is often limited, and many patients with painful DPN still use opioids.

About Helixmith Co., Ltd.

Helixmith is a clinical-stage gene therapy companybased in Seoul and San Diego, developing new and innovative biopharmaceuticals to tackle previously untreated diseases. The company has an extensive gene therapypipeline, including a CAR-T program targeting several different types of solid cancers and an AAV vector program targeting neuromuscular diseases. Engensis (VM202), the most advanced pipeline candidate, is a plasmid DNA therapy being studied for diabetic peripheral neuropathy, diabetic foot ulcers, claudication, amyotrophic lateral sclerosis, coronary artery disease, and Charcot-Marie-Tooth disease. The company is listed on KOSDAQ.

SOURCE Helixmith USA Inc.

More:
Paper Reporting Results from Helixmith's Phase 3 Gene Therapy Trial for Painful Diabetic Neuropathy was One of the Top-10 Most-Downloaded Articles in...

CAMBRIDGE, Mass., March 16, 2022 /PRNewswire/ -- Alltrna, a Flagship Pioneering company unlocking transfer RNA (tRNA) biology and pioneering tRNA therapeutics to regulate the protein universe and resolve disease, today announced the formation of Alltrna's Scientific Advisory Board (SAB) with leading experts in RNA biology and therapeutics. The SAB will work closely with Alltrna's leadership team as they map tRNA biology to systematically design tRNA medicines and encode a completely new, unifying approach to treating both rare and common human diseases driven by shared genetic mutations.

To watch the full video, click here.

"We are honored to have these remarkable and accomplished scientific leaders join Alltrna's Scientific Advisory Board," said Lovisa Afzelius, Ph.D., Origination Partner at Flagship Pioneering and Founding CEO of Alltrna. "Each person has made significant contributions and pioneered breakthroughs in RNA research and therapeutics, and together, they will be a powerhouse of expertise and experience for Alltrna, as we leverage our deep understanding of tRNA biology and its diverse combinatorial modifications to systematically design, program, and deliver tRNAs to correct disease."

"I've been working closely with Alltrna over the past couple years as the team has built a truly remarkable platform to unlock the entire tRNA biology space with an unprecedented therapeutic opportunity to help millions of patients with both rare and common diseases," said Rachel Green, Ph.D., Chair of Alltrna's SAB. "I'm delighted that these world leaders in RNA biology and therapeutic development have joined Alltrna's SAB at this pivotal time in the company's growth and look forward to working together to help Alltrna realize the enormous potential of tRNA biology as a novel framework and source for new programmable medicines."

Alltrna Scientific Advisory Board Members

Story continues

Rachel Green, Ph.D., Chair, is an investigator at the Howard Hughes Medical Institute (HHMI) and a Bloomberg Distinguished Professor in the Department of Molecular Biology and Genetics at the Johns Hopkins University School of Medicine. During her doctoral research at Harvard Medical School, Dr. Green developed in vitro selection approaches that are broadly used for the analysis of functional RNAs in many systems. Her current research focuses on mechanisms of mRNA translation and its regulation. Dr. Green is an elected member of the American Academy of Arts and Sciences (AAAS) and the National Academy of Sciences (NAS). In addition to Alltrna, she serves on the SAB for Moderna and Initial Therapeutics.

Tracy Johnson, Ph.D., is a HHMI Professor and Dean of Life Sciences and Senior Associate Dean at the David Geffen School of Medicine at UCLA. She has more than 25 years of experience studying the biochemistry of RNA. Her laboratory utilizes a combination of molecular genetics, bioinformatic, and biochemical approaches to understand mechanisms of gene regulation, particularly RNA splicing and chromatin modification, and the intersection between these reactions. Dr. Johnson has received numerous awards, including the National Science Foundation's CAREER and PECASE awards and the 2022 Ruth Kirschstein Diversity in Science Award from the American Society for Biochemistry and Molecular Biology.

Anastasia Khvorova, Ph.D., is a Professor in the RNA Therapeutics Institute and Program in Molecular Medicine at the University of Massachusetts (UMass) Chan Medical School, where her lab develops novel approaches and solutions to understanding natural and therapeutic RNA trafficking and delivery. She founded the UMass Nucleic Acid Chemistry Core, the only nonprofit facility in North America capable of gram-scale synthesis of modified oligonucleotides. Prior to UMass, Dr. Khvorova served as Chief Scientific Officer at Dharmacon, ThermoFisher, and RXi Pharmaceuticals. She is inventor on more than 150 patents and 200 patent applications and has authored more than 50 peer-reviewed publications, defining the field of RNAi drug design and development.

Melissa Moore, Ph.D., is the Chief Scientific Officer, Scientific Affairs at Moderna, where she leads mRNA biology, delivery, and computation science research. Previously, she was a Professor of Biochemistry & Molecular Pharmacology and a HHMI Investigator at the UMass Chan Medical School, where she was instrumental in creating a faculty-led program to facilitate the translation of discoveries into drugs, products, technologies, and companies. Her 23-year career in academic research focused on the roles of RNA and RNA-protein complexes in regulating gene expression, and her research touched on many human diseases. Dr. Moore is an elected member of AAAS and NAS, and she received the RNA Society Lifetime Achievement Award in 2021.

About Alltrna

Alltrna unlocks tRNA biology to correct disease. The company's platform incorporates AI/ML tools to learn the tRNA language and deliver diverse programmable molecules with broad therapeutic potential. Alltrna has an unprecedented opportunity to advance a single tRNA medicine to unify treatment across a wide range of diseases with the same underlying genetic mutation. Alltrna was founded in 2018 by Flagship Pioneering. For more info, visit http://www.alltrna.com.

About Flagship Pioneering

Flagship Pioneering conceives, creates, resources, and develops first-in-category bioplatform companies to transform human health and sustainability. Since its launch in 2000, the firm has, through its Flagship Labs unit, applied its unique hypothesis-driven innovation process to originate and foster more than 100 scientific ventures, resulting in more than $140 billion in aggregate value. To date, Flagship has deployed over $2.6 billion in capital toward the founding and growth of its pioneering companies alongside more than $19 billion of follow-on investments from other institutions. The current Flagship ecosystem comprises 42 transformative companies, including Axcella Health (Nasdaq: AXLA), Codiak BioSciences (Nasdaq: CDAK), Denali Therapeutics (Nasdaq: DNLI), Evelo Biosciences (Nasdaq: EVLO), Foghorn Therapeutics (Nasdaq: FHTX), Indigo Ag, Kaleido Biosciences (Nasdaq: KLDO), Moderna (Nasdaq: MRNA), Omega Therapeutics (Nasdaq: OMGA), Rubius Therapeutics (Nasdaq: RUBY), Sana Biotechnology (Nasdaq: SANA), Seres Therapeutics (Nasdaq: MCRB), and Sigilon Therapeutics (Nasdaq: SGTX).

Media Contact for AlltrnaJessica Yingling, Ph.D., Little Dog Communications Inc., jessica@litldog.com, +1.858.344.8091

(PRNewsfoto/Alltrna)

Cision

View original content to download multimedia:https://www.prnewswire.com/news-releases/alltrna-announces-formation-of-scientific-advisory-board-with-world-leading-rna-experts-301503360.html

SOURCE Alltrna

Read the original post:
Alltrna Announces Formation of Scientific Advisory Board with World-Leading RNA Experts - Yahoo Finance

Before March 2020, many people saw pandemics as a thing of the past. Then came COVID-19. Scientists still do not know exactly where the virus that caused it SARS-CoV-2 came from, but it soon reached almost every country worldwide. Over 2 years, the virus has evolved, producing several variants. In this Special Feature, we look at the evolution of SARS-CoV-2 and ask what lessons scientists have learned.

In late 2019, there was a sudden increase in pneumonia cases in central China. By January 7, scientists had identified and isolated a previously unknown coronavirus, now designated SARS-CoV-2.

On March 11, 2020, the World Health Organization (WHO) declared COVID-19 a pandemic.

Now, 2 years on, authorities have recorded more than 458 million cases of COVID-19, the disease resulting from SARS-CoV-2. The disease has also played a role in the deaths of more than 6 million people.

However, the actual death toll may well be far higher than 6 million. According to a recent paper in The Lancet, the actual death toll may be at least three times that.

On December 29, 2019, experts linked four cases of pneumonia of unknown etiology to the Huanan Seafood Wholesale Market in Wuhan, central China.

On January 7, 2020, researchers isolated the causative agent, SARS-CoV-2, and on January 10, they sequenced its genome.

By January 2, 2020, doctors had confirmed that 41 people in a Wuhan hospital with severe respiratory illness had a SARS-CoV-2 infection. Of these individuals, 27 had had exposure to the seafood market.

Many coronaviruses exist, affecting both animals and people. Most cause infections with mild to moderate symptoms in the upper respiratory tract, such as colds.

In recent years, two coronaviruses SARS-CoV and MERS-CoV have caused more severe disease. SARS-CoV, which scientists identified in November 2002, was responsible for severe acute respiratory syndrome (SARS), which emerged in Asia. The Centers for Disease Control and Prevention (CDC) note that of the 8,096 people with a known SARS infection, 774 died. There have been no reported cases since 2004.

Scientists first identified Middle East Respiratory Syndrome (MERS), the disease that MERS-CoV-2 causes, in 2012 in Saudi Arabia. The mortality rate for MERS is high of every 10 people with the infection, three or four die. There continue to be occasional, localized outbreaks of this disease.

Both of these coronaviruses caused diseases with high fatality rates, but it was possible to contain the spread before they reached pandemic levels. So, were we ready for the next coronavirus?

Experts believe that SARS came from bats and that MERS crossed over to people from camels. However, for SARS-CoV-2, researchers have not all agreed on any of the many existing theories.

At first, people thought that SARS-CoV-2 might have come directly from bats. Scientists discounted that theory, though, as the spike protein on SARS-CoV-2 is very different from that on the coronaviruses present in bats.

Now, researchers think it is likely that the virus originated in bats but had an intermediate host between bats and people. A recent study which has not yet undergone peer review suggests that live mammals for sale at the Huanan Seafood Wholesale Market in Wuhan, the epicenter of early cases, might have been the intermediate host.

Another recent study also yet to undergo peer review that analyzed the evolution of SARS-CoV-2 suggests that SARS-CoV-2 emergence likely resulted from multiple zoonotic events. The researchers do not suggest what the intermediate animal hosts might be.

Alternatively, did SARS-CoV-2 escape from a laboratory in Wuhan, as some media outlets have suggested? The WHO has dismissed this theory as extremely unlikely.

So, there is still uncertainty about the origins of SARS-CoV-2. And this may be due, in some measure, to a lack of international cooperation, as Prof. Jonathan Stoye, a virologist at the Francis Crick Institute in London, United Kingdom, told Medical News Today.

In his opinion, one mistake was to start pointing fingers at China and blaming them for the origin of this virus. I think that, naturally, led to pushback from the Chinese [authorities].

He added: I absolutely believe in natural origins [of SARS-CoV-2], but the Chinese [authorities] could have made things easier if theyd opened up their books straightaway. They werent going to do that when they were being accused of being responsible [for the virus].

For almost a year, the original Wuhan variant of SARS-CoV-2 moved across the globe. Then, in late 2020, the number of COVID-19 cases increased rapidly in South East England, in the United Kingdom.

Researchers discovered that a new variant, which was 50% more transmissible than the original and had 17 unique mutations, was responsible. In December 2020, the WHO designated it B.1.1.7, or the Alpha variant.

Scientists have since identified many other variants, but the WHO has only designated five as variants of concern (VOC). The VOCs and the location of their initial identification are:

Each variant has different features. Some variants are more transmissible than others, and some are more virulent. It is these features that have caused the multiple waves of COVID-19.

The regular and rapid emergence of new variants in the past 2 years have made the course of the pandemic very unpredictable.

Dr. Arturo Casadevall, distinguished professor and chair of molecular microbiology and immunology and infectious diseases at the Johns Hopkins Bloomberg School of Public Health in Baltimore

Viruses mutate all the time. Each time they replicate, which they do frequently, their genetic material is copied. A mutation happens when part of the genetic material is copied incorrectly.

In a coronavirus, the genetic material is ribonucleic acid (RNA). An enzyme called RNA polymerase controls the replication, and it often makes errors. Most mutations create a virus that cannot replicate and spread among people. However, some mutations lead to a virus that can replicate: a variant.

A mutation might give the virus a selective advantage, such as better transmissibility or greater virulence. If it is more transmissible, the variant may spread faster and outcompete previous variants. This is what happened with the Alpha, Delta, and Omicron variants of the coronavirus.

Some situations give viruses more opportunities to mutate, as Dr. Christopher Coleman, assistant professor of infection immunology at the University of Nottingham, U.K., explained to MNT:

Viruses naturally mutate as they replicate, so in an immunocompromised host where the virus replicates more easily, there will be a correspondingly increased number of mutations.

Omicron has more than 50 mutations, of which some 30 are in the spike protein that the virus uses to gain entry to host cells. One theory suggests that it may have evolved in people with HIV, a virus that suppresses the immune system.

Moving between host species also increases the mutation rate. Dr. Coleman added that the [i]nfection of animals by humans will mean the virus then adapts to a new host, which involves mutations.

Domestic animals, such as cats, dogs, and ferrets, have had SARS-CoV-2 infections. The CDC notes that on one mink farm in Michigan, several animals contracted the virus, which then passed back to workers. On testing, the viral samples from the workers contained several mink-related mutations.

You are getting evolution occurring from different starting points. Whether they are occurring through immunosuppressed or immunocompromised patients, or whether they are happening through animals, or how, I dont know that we know, and I dont know that we will ever really know.

Prof. Jonathan Stoye

Decades of research into coronaviruses led to the rapid development of vaccines, many of them using new technologies. These have been incredibly effective in reducing the impact of COVID-19 and allowing society to regain some measure of normality.

But, as Prof. Stoye explained, [i]n retrospect, we have been lucky that it has been possible to make a vaccine against this particular virus, whereas for things like HIV [], we still dont have vaccines.

However, vaccines designed against one variant might be ineffective against another.

The evolution of SARS-CoV-2 variants upended many optimistic predictions made when the vaccines were rolled out in 2020.

Dr. Arturo Casadevall

Despite the evolution of variants, vaccines still guard against severe COVID-19, particularly in those who have received multiple vaccinations.

Despite suggestions that vaccines might even drive the evolution of new vaccine-resistant variants, this does not seem to be the case, as a recent report states: Given the emergence of immunity-evading variants even before vaccines were broadly deployed, it is hard to implicate vaccines or vaccine deployment strategies as the major drivers of immune evasion.

Prof. Stoye feels that vaccines will continue to be important. I suspect we will have to have yearly boosters of the vaccine, at least for the foreseeable future, he said.

And he expressed a hope that research might create more powerful vaccines:

It would be very nice if scientists could establish a pan-coronavirus vaccine that worked against multiple viruses. That has to be one of the hopes of the future that you will have a method of vaccination that will protect you against various viruses.

After 2 years, people are becoming tired of restrictions, feeling that the pandemic should surely be over. However, Prof. Stoye is one of many experts expressing concern that governments are removing COVID-19 testing and control measures too early.

One of the things Im frightened about is that we will, in fact, lose our ability to follow these processes as we stop testing and sequencing so much. [] As we test less, as we sequence less, we will lose that ability to recognize new variants in real time, he told us.

These things will come again. We need to realize that, and we need to have a response ready quickly. I think we need to be able to recognize very rapidly the appearance of new diseases this comes back to geopolitics.

Prof. Jonathan Stoye

This is not the first pandemic, and it is unlikely to be the last. Some aspects have been well-handled, while others have not, and the geopolitical debates will continue for years. At least vaccines are continuing to protect against severe illness and death from all variants.

Possibly the most important lesson is that it is crucial to address future disease outbreaks globally. Although people in high income countries have had ready access to vaccines and boosters, many African countries have yet to vaccinate even 10% of their population due to inequitable vaccine distribution.

The lack of widespread vaccination can also contribute to the development of new variants.

Prof. Stoye stressed the importance of global cooperation in countering pandemics:

The global aspects of this are the interesting and important ones. Whether those lessons will be learned, I dont know. [] I would hate to think that, suppose in 2 or 3 years down the track, we are living comfortably with this virus, and SARS-3 comes along or HIV5, and we have forgotten all the lessons we have learned. Its trying to retain that memory that is the important lesson.

For live updates on the latest developments regarding COVID-19, click here.

More:
2 years of COVID-19: Origins, variants, and the future - Medical News Today