Category Archives: Transhuman News

Plant genetics research at the University of Georgia spans schools, departments, disciplines, and centers. From the College of Agricultural and Environmental Sciences (CAES) to Franklin College of Arts and Sciences, the Plant Center to the Institute of Plant Breeding, Genetics & Genomics and more, UGA faculty with genetics expertise are seeking plant-based solutions to societal challenges. (Photo by Andrew Davis Tucker)

ATHENS -- With record-breaking temperatures and extreme weather escalating, the threats posed by climate change are intensifying. But the plants of tomorrow small and humble though they might be could help us meet the massive challenges of our warming planet.

Plant genetics research at the University of Georgia spans schools, departments, disciplines, and centers. From the College of Agricultural and Environmental Sciences to Franklin College of Arts and Sciences; from the Plant Center to the Institute of Plant Breeding, Genetics & Genomics and more, UGA faculty with genetics expertise are seeking plant-based solutions to societal challenges.

Some of these faculty are conducting studies at the cellular level, while others investigate plants as whole organisms. Still others are exploring how epigenetics shape entire ecosystems. And while a number of UGA geneticists prioritize fundamental discovery, others are partnering with breeders or with industry to bring new crops and plant-based products to market.

Were spread out all over campus, Bob Schmitz, UGA Foundation Professor of Plant Sciences and the Lars G. Ljungdahl Distinguished Investigator of Genetics, said. But we all speak the same language."

Growing up in Minnesota, Distinguished Research Professor John Burke took an interest in the outdoors, collecting snakes, salamanders, and turtles with his two older brothers. Years later, he earned his Ph.D. in genetics from UGA and returned as a faculty member in 2006. Among his many studies, he has put particular focus on sunflowers.

Schmitz likes to tell people that hell work on any plant that has DNA which is all of them, of course. Our questions are broader than any particular plant, he said.

A member of the Department of Genetics in the Franklin College of Arts and Sciences, Schmitz studies the mechanisms of epigenetic inheritance in plants, or how a plants environment influences the way its genes operate.

Members of the Schmitz Lab, working in partnership with international researchers, discovered that rare changes to DNA methylation can spuriously occur over generations of plants. They then found that they could use those multigenerational changes, which tick at a constant rate, to determine plant divergence time.

The information provided by this epigenetic clock, Schmidtz says, includes data relevant to the timing of invasive species introduction and the impact of human activity on native environments. These insights could prove useful for understanding how plant populations migrate, expand, or contract due to a changing climate.

Passing along fundamental genetic discoveries to research partners along the basic-to-applied continuum is something UGA does well, John Burke, a distinguished research professor and head of the Department of Plant Biology in the Franklin College of Arts and Sciences, said. He notes that the broad intersectionality of plant research has become a signature strength of the university.

There are intentional mechanisms in place to help bridge gaps between units, Burke said. We have ways to work together here. Thats critically important.

While some UGA plant geneticists pursue fundamental discovery, others are bridging the gap between basic and applied research. From Crop & Soil Sciences to Plant Pathology and Horticulture within the College of Agricultural and Environmental Sciences, these faculty members are helping transform crop plants, native species, and the future of bioenergy for a changing global climate.

As the Georgia Research Alliance Eminent Scholar Chair in Crop Genomics, Robin Buell uses comparative genomics, bioinformatics, and computational biology to investigate the genome biology of plants and plant pathogens. While her subjects have ranged from rice and potatoes to maize, switchgrass, and medicinal plants, she currently studies poplar. Buell is the principal investigator on a $15.8 million Department of Energy grant to genetically engineer poplar trees (Populus sp. and hybrids) for biofuel production and other uses.

Poplar has strong potential to provide an alternative to petroleum-based products, Buell explains.

Its so fast-growing, its almost a weed," she said. "You can grow it almost everywhere. You dont have to grow it on prime land. Weve been able to do genetic engineering for the last 20 years, active breeding for even longer. But those developments have been incremental, not substantial.

This project has a more audacious goal.

Lets reinvent this tree, she said. Lets take Humpty Dumpty, lets break him, and lets put him back together again, but in a more intelligent way and faster.

The redesigned poplars will be fabricated through an intensive process that begins with measuring mRNA transcripts and includes mapping gene function throughout the tree. The end result could provide an alternative fuel for jet engines, among other sustainable products.

Wayne Parrott, distinguished research professor of crop and soil sciences, calls his area of investigation Biotechnology 2.0. An internationally renowned geneticist, Parrott has spent more than 35 years at UGA leveraging tools to help new soybean varieties and investigating the environmental and human safety of genetically modified crops.

My lab focuses on the development and use of biotechnology applications to help out with conventional plant breeding and plant improvement, he said. But theres a lag between what people want to do and what people are able to do.

His team is closing that gap by developing biotechnology applications to help strengthen conventional crop plant breeding and improvement.

Parrott directs the Institute for Plant Breeding, Genetics & Genomics, where researchers from multiple disciplines develop new crop varieties and conduct studies to understand the genetic traits of plants important to agriculture and humankind. He credits the institute with helping bring together plant genetics experts from all positions along the research pipeline.

Esther van der Knaap is a distinguished research professor of horticulture in the College of Agricultural and Environmental Sciences. She describes Integrated Plant Sciences as a central access point for prospective students to plant and fungal research across UGA. The curriculum allows students to undertake rotations in their first year to determine the best fit for their research interests, whether bioinformatics, ecology, genetics, breeding, biochemistry or some combination.

This type of program is something I dreamed about at my previous institution, but it wouldnt have been possible, van der Knaap said. At UGA, it was possible.

Van der Knaaps own research involves tomato foodshed. At the Center for Applied Genetic Technologies, which supports the development, application, and commercialization of new technologies to genetically improve crops, the van der Knaap lab studies variations in tomato fruit quality, from shape and size to taste. The latter trait is closely connected to aroma and especially important for fresh market tomatoes.

Van der Knaaps team is collaborating with food scientists, breeders, and biochemists at UGA and at the University of Florida to identify genes that cause variations in the flavor profile of tomato as they became domesticated over time, from fully wild to what we buy in grocery stores today. The resulting information about genes that improve flavor can be used by breeders to develop tastier tomatoes for the market.

Our focus is on capturing the genes that control fruit quality traits in tomato, she said. We also investigate the genetic diversity of these genes that, collectively, offer knowledge to breeders in both public and private sectors.

A new frontier in plant genetics research is high-throughput phenotyping, a type of genetic screening that uses cutting-edge technologies to generate data about large plant populations such as a crop field or forest. Guoyu Lu, an assistant professor in the School of Electrical and Computer Engineering and a specialist in high-throughput phenotyping, says that these new technologies could help researchers, breeders, farmers, and forestry officials make decisions in real time to support and protect the plants they oversee.

Lu comes to this work with a track record of engineering innovation. Before joining the UGA faculty in 2022, his career included positions as a research scientist on autonomous driving at Ford and a computer vision engineer at the Disney ESPN Advanced Technology Group. His projects have attracted the interest and investment of Ford, GM, Qualcomm, Tencent, Mackinac and more.

I work on the AI side, Lu said. Im an AI scientist, but Im developing algorithms for plant scientists.

Using computer vision and robotics, including unmanned aerial vehicles, Lu and his team are capturing and generating data on specific genetic traits within large plant populations. The information they gather includes root structure, height, disease state, and more all collected without harming the plants themselves.

Currently, Lu is working to build an AI algorithm that is one-size-fits-all a multipurpose tool suitable for gathering genetic data on many different plants across multiple populations. He wants that tool to be accessible to anyone who needs it in the field, especially as extreme weather patterns intensify.

My work uses UAV to estimate the 3D structure models of both crops and forests, he said. The 3D structures can provide height, coverage, and other information. This data can be used to estimate growth, carbon dioxide absorption, impact on the environment, and more.

Plant genetics at UGA begins and ends with partnerships. Researchers have forged ties across disciplines and schools, with strong collaboration from field sites and with sustained support from leaders and partners across Georgia and beyond.

We have some of the top researchers in the world right here at UGA, Burke said. And the work is going on across the spectrum.

The race to adapt to a changing climate is on and these scientists are leading the way, with bold inquiry and deep appreciation for the plants they have dedicated their professional lives to understanding and championing.

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UGA plant geneticists are tackling the climate crisis - Longview News-Journal

Letzte Aktualisierung: June 25, 2024

The Belgian EU Council Presidency is once again attempting a compromise on the deregulation of new genetic engineering techniques. Read Table.Briefings to find out how the chances of success are assessed.

A few days before Hungary takes over the Presidency of the EU Council of Ministers, the outgoing Belgian Council Presidency wants to make one last attempt to reach an agreement on the deregulation of new genetic technologies (NGT). According to diplomatic sources, the Belgians want to present a compromise proposal to the EU ambassadors on Wednesday. There was not enough time to put the issue on the agenda of the EU Agriculture Council on Monday. It is the last regular meeting of the responsible ambassadors before the end of the Presidency.

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According to latest report, the global genome editing market size was USD 8.45 billion in 2023, calculated at USD 9.88 billion in 2024, and is expected to reach around USD 40.48 billion by 2033, expanding at a CAGR of 16.96% from 2024 to 2033, North America dominated the market with the largest revenue share of 49% in 2023.

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Gene editing technologies, such as CRISPR-Cas9, TALENs, ZFNs, and meganucleases, represent pivotal advancements enabling scientists to enhance the characteristics of organisms ranging from plants to animals and bacteria. These technologies function akin to molecular scissors, precisely cutting DNA at targeted locations and facilitating the removal, addition, or replacement of specific DNA sequences. By altering DNA, scientists can modify physical traits like eye color and mitigate disease risks, thereby expanding the applications of genome editing across various sectors. The continuous development and application of these technologies are pivotal in driving growth within the genome editing market, fostering innovation and broader adoption across scientific and industrial domains.

Genome editing using clustered regularly interspaced short palindromic repeats (CRISPR) has revolutionized the ability to precisely and efficiently modify DNA within cells. This technique involves the Cas9 protein, guided by RNA, targeting specific DNA sequences and inducing cuts at precise locations marked by protospacer adjacent motif (PAM) sequences. These cuts enable scientists to disable or alter DNA sequences, facilitating precise modifications such as edits to genetic sequences or adding/removing sections of DNA.

Genome editing holds immense potential to transform cellular and organismal characteristics, offering applications across various fields including agriculture, medicine, and biotechnology. The continuous advancement and adoption of CRISPR-based technologies are key drivers propelling rapid growth within the genome editing market, fueling innovation and expanding possibilities for genetic manipulation and therapeutic applications.

Key Takeaways:

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U.S. Genome Editing Market Size and Growth

The U.S. genome editing market size was valued at USD 4.14 billion in 2024 and is projected to surpass around USD 16.49 billion by 2033, registering a CAGR of 16.6% over the forecast period of 2024 to 2033.

North America has emerged as a dominant force in the genome editing market, driven by strong public support and significant scientific advancements in CRISPR technology. Americans are increasingly receptive to gene editing techniques for therapeutic applications, particularly in treating heritable blood disorders like sickle cell anemia, as evidenced by promising clinical trial outcomes. This optimism, public opinion reflects a nuanced perspective on the ethical implications of gene editing for disease prevention in babies. A majority believes that widespread adoption of gene editing could lead to societal pressures for parents to utilize these technologies to mitigate disease risks in offspring. This regional landscape underscores North America's pivotal role in shaping the future of genome editing through technological innovation and evolving public discourse on ethical considerations.

Asia Pacific is anticipated to witness the fastest growth at a CAGR of 18.75% from 2024 to 2033, driven by significant opportunities in crop improvement and agricultural innovation. With more than half of the world's population residing in the region, there is a pressing need for sustainable agricultural practices to ensure food security. Genome editing technologies offer a promising solution by enabling precise modifications to crop genomes, enhancing traits such as yield, disease resistance, and nutritional content. Countries in Asia Pacific, including India, are keenly adopting genome editing to tailor agricultural products to meet specific demands.

Institutions like the National Agri-Food Biotechnology Institute (NABI) are pioneering efforts in applying genome editing tools to a wide range of crops such as banana, rice, wheat, tomato, and millet. This proactive approach positions Asia Pacific as a hub for innovation in agricultural biotechnology, fostering partnerships and research collaborations aimed at harnessing the full potential of genome editing to address regional food challenges and promote sustainable agriculture.

U.S. Genome Editing Market Trends

The presence of robust research infrastructure, a rise in genetically modified crops, and an increase in the prevalence of genetic diseases are some of the major factors boosting the U.S. genome editing markets growth. Moreover, in the U.S., genetic diseases such as cystic fibrosis are prevalent. On the other hand, a rise in the number of patent approvals for U.S.-based companies has also accelerated the adoption of genome editing tools in the country, leading to positive market growth. Further, with increased government funding and support for scientific R&D, the U.S. held the largest market share for genome editing technology in North America.

Europe Genome Editing Market Trends

The genome editing market in Europe was identified as lucrative. This is attributed to the adoption of new rules related to genome editing by European countries creating an opportunity for the market.

The UK genome editing market presents several potential opportunities that favor an increase in the usage of advanced genome editing tools. Numerous efforts undertaken by UK-based genome editing companies and funding initiatives supported by private & public entities drive the UK markets growth. In September 2021, the UKS Department for Environment, Food and Rural Affairs (Defra) declared that by the end of 2021, researchers who wanted to conduct field trials of gene-edited plants will no longer be required to submit risk assessments.

The genome editing market in France growth is driven by the rising prevalence of hereditary diseases, such as hemophilia and metabolic disorders. To cure such disorders, several researchers are using genome editing technologies. Furthermore, France is undertaking several efforts to drive innovation in plant genetics, thereby boosting market growth in the country. Some of the 28 leading private and public research organizations involved in plant breeding, plant science, and connected technologies formed the Plant Alliance.

The Germany genome editing market generated significant revenue in Europe in 2023, which can be attributed to the presence of developed global companies, such as Merck KGaA & QIAGEN, which offer genome editing and related products. The collaboration and partnership models among key players strengthen their market presence in the country as well as at a global level, hence, driving the revenue in the country.

Asia Pacific Genome Editing Market Trends

Asia Pacific is anticipated to witness the fastest growth at a CAGR of 18.75% from 2024 to 2033. The regional market growth is expected to be driven by the increasing demand for gene editing technologies and the rising prevalence of genetic disorders and diseases across countries like India and Australia. Moreover, the domestic companies providing gene editing products and services are attracting investments and funding. For instance, in April 2021, GenScript launched Research-Grade Lentiviral Vector Packaging Service for drug discovery, cell line development, and gene editing.

The China genome editing market is growth is driven by the local presence of key market players, such as GenScript. The company is taking initiatives to promote genome engineering services such as CRISPR services and gene services. The China market for genome editing is ready for growth due to the Chinese government's increasing focus on precision medicine and the presence of major players such as BGI, and Hebei Senlang Biotechnology.

The genome editing market in Japan is characterized by an increasing number of Japanese companies that are acquiring licenses to the CRISPR-Cas9 technology, potentially driving market growth. In addition, an increasing prevalence of genetic diseases and diabetics coupled with growing genomic research initiatives is expected to drive the market in Japan. In Japan, around 13.5% of the total population either has type 2 diabetes or impaired glucose tolerance.

The India genome editing market is expected grow in the near future. India possesses a high growth potential due to the high competency and intense demand for genome editing technology to improve agriculture productivity suitably. In the country, the Department of Biotechnologys (DBT) National Agri-Food Biotechnology Institute is utilizing CRISPR genome editing technology to modify bananas. Moreover, ongoing research projects related to CRISPR/Cas9 by Indian researchers and scientists are expected to drive the market growth.

Middle East And Africa Genome Editing Market Trends

The genome editing market in Middle East and Africa is projected to grow in the forthcoming years. The increasing applications of biotechnology in healthcare are contributing to the expansion of the market in this region.

The Saudi Arabia genome editing market is characterized by several ongoing research projects related to CRISPR genome editing technology which are expected to boost the market growth over the forecast period. The rising adoption of CRISPR technology for enhancing the immune system of plants is expected to drive market growth in the coming years.

The genome editing market in Kuwait is expected to witness rapid growth in the coming decade due to the increasing investment in scientific R&D, both by the government and private sector, which drives innovation in genetic technologies. This investment creates opportunities to develop new and improved genome editing tools and techniques.

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Market Dynamics

Driver

Versatile Genome-Editing Technologies

The emergence of highly versatile genome-editing technologies, such as CRISPR-Cas9, TALENs, ZFNs, and engineered Cas9 nickases, has revolutionized the ability to make precise, sequence-specific modifications in a wide range of cell types and organisms economically and swiftly. Recent advancements, including single-base editing without DNA breaks and self-inactivating vectors that link genomic modifications to self-degradation, promise enhanced specificity in editing. This potential reduction in off-target effects is critical as it correlates with the duration of cellular exposure to nucleases. These innovations are poised to fuel growth in the genome editing market by addressing key challenges and expanding therapeutic applications in clinically relevant settings.

Restraint

Challenges in Long-term Expression of Genome Editing Tools

Genome editing tools ideally require transient expression in target cells to mitigate risks of off-target nuclease genotoxicity and immune responses to prokaryotic proteins. Advancements and hundreds of therapies in clinical trials, the high costs associated with these treatments, often around US$1 million per procedure plus additional expenses for hospitalization and procedural complexities, pose significant barriers. These financial implications limit broader adoption and growth of the genome editing market, necessitating innovations to streamline costs and enhance accessibility for wider patient populations.

Opportunity

Advancements in HDR-Mediated Gene Editing

Precise genome editing, crucial for both preclinical research and clinical gene therapy, has traditionally relied on HDR (homology-directed repair). Recent efforts to enhance HDR efficiency include using rationally designed single-stranded oligodeoxynucleotide (ssODN) templates and employing NHEJ (non-homologous end joining) inhibitors. The delivery of Cas9 and HDR templates via AAVs has successfully achieved precise genome editing in post-mitotic neurons and cardiomyocytes. These advancements, HDR-mediated editing efficiency remains lower compared to the more predominant NHEJ pathway, which can introduce unintended genomic alterations. Addressing these challenges presents significant opportunities for innovation and growth within the genome editing market, particularly in enhancing HDR-mediated techniques and minimizing off-target effects.

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Report Highlights

By Technology Insights

The CRISPR/Cas9 segment held the largest market share of 43.89% of the global revenue in 2023, holding the largest market share due to its remarkable efficiency, precision, and versatility across various disciplines. Adapted from bacteria's natural immune defense mechanism against viruses, CRISPR/Cas9 enables precise modifications to DNA by using guide RNA (gRNA) to target specific genetic sequences. The Cas9 enzyme then cleaves the DNA at the targeted site, initiating the repair process that allows for editing genetic material in living cells. This revolutionary technology operates through a streamlined process of recognition, cleavage, and repair, offering researchers unprecedented capabilities to edit genes in a wide array of organisms and applications. Its adaptability has spurred innovation in agriculture, medicine, biotechnology, and beyond, making CRISPR/Cas9 a pivotal tool for advancing scientific research and addressing complex genetic challenges. As research continues to refine and expand the applications of CRISPR/Cas9, it remains at the forefront of genome editing technologies, driving significant developments and market growth worldwide.

The ZFN segment is expected to witness a substantial CAGR of 16.56% over the forecast period, driven by their role as precise gene-targeting tools. ZFNs function by inducing targeted double-strand breaks in DNA, which trigger cellular repair mechanisms capable of introducing specific mutations or replacing genes with high efficiency. Initially developed as a gene-targeting technology, ZFNs have evolved to find applications across various organisms and genetic contexts. Advancements in designing zinc-finger sets for new genomic targets, refining the design and selection processes remains an ongoing area of development. This technology's capability to facilitate targeted mutagenesis and gene replacement at high frequencies underscores its potential in advancing research and therapeutic applications. As methodologies continue to improve, ZFNs are expected to play a pivotal role in precision medicine, agriculture, and biotechnology, contributing to significant advancements and market expansion in genome editing technologies globally.

By Delivery Method Insights

The ex-vivo segment dominated the market with a share of 51.65% in 2023 the genome editing market, capturing a significant share. Ex vivo genome editing involves editing the genome of specific cells outside the body (in vitro), followed by the transplantation of these modified cells back into the patient to achieve therapeutic outcomes directly linked to the genetic modification. This approach offers distinct safety advantages, particularly in minimizing off-target gene editing risks, as the editing occurs in isolated cells under controlled laboratory conditions before reintroduction into the patient. Ex vivo genome editing is pivotal in advancing personalized medicine, as it allows for precise modifications tailored to individual genetic profiles. With ongoing advancements in technology and methodologies, ex vivo approaches are poised to drive further innovations in therapeutic applications, bolstering their prominence in the evolving landscape of genome editing delivery modes.

The in-vivo segment is projected to witness the fastest growth at a CAGR of 19.94% from 2024 to 2033 to advancements in technology that enable targeted gene modifications directly within the body. This approach eliminates the need for ex vivo manipulation of cells and offers potential benefits in terms of treatment efficiency and safety. Endonuclease-based strategies have shown promise in correcting diseases by targeting specific genes, driving ongoing research and clinical trials aimed at enhancing the therapeutic potential of in vivo genome editing across various genetic disorders. As these technologies continue to evolve and regulatory frameworks adapt, the in vivo segment is poised to play a pivotal role in shaping the future of genetic medicine.

By Application Insights

The genetic engineering segment held the largest market share in 2023 in genome editing, leveraging technologies that enable precise modifications to an organism's DNA. These tools facilitate the addition, removal, or alteration of genetic material at specific locations within the genome. One prominent approach is based on adapting bacterial immune defense systems, where RNA guides with specific sequences bind to targeted DNA sequences, akin to how bacteria use CRISPR arrays. This method enables researchers to edit DNA effectively and has widespread applications across various fields, driving innovation and growth in the genetic engineering market.

The clinical applications segment is expected to grow at a significant CAGR of 13.19% over the forecast period, particularly in germline genome editing, which involves modifying genetic material in germ cells and embryos. Unlike somatic genome editing, changes made in germline cells can be inherited by future generations. This approach holds promise for addressing genetic disorders and enhancing traits in offspring, with ongoing research exploring diverse targets and therapeutic purposes. As technologies advance, the application of genome editing in clinical settings continues to expand, driving forward new possibilities and advancements in genetic medicine.

By Mode Insights

The contract segment has emerged as the dominant force in the market, driven by genome editing technologies such as CRISPR/Cas. These advancements have significantly expanded the capabilities and efficiency of modifying genetic material in organisms. Genome editing is increasingly utilized to introduce agriculturally beneficial traits and genetic combinations in plants and animals. Contract services offer specialized expertise and resources to facilitate these genetic modifications, meeting the growing demand for tailored genetic solutions across agricultural sectors. This trend underscores the pivotal role of contract services in advancing genome editing applications for agricultural innovation and productivity enhancement.

The in-house segment is expected to grow at a CAGR of 13.4% from 2024 to 2033. This trend is driven by the adoption of in-house genetic counseling services, particularly in prenatal care settings. Studies have shown that integrating genetic counseling conducted by experienced professionals such as geneticist-obstetricians with expertise in prenatal ultrasound can notably enhance the detection rates of abnormal karyotypes. This approach provides healthcare facilities and institutions with greater control and customization over genetic counseling services, ensuring more effective prenatal care and diagnostic outcomes. As demand for personalized genetic counseling grows, the in-house model offers advantages in terms of efficiency, continuity of care, and enhanced patient outcomes, thereby fueling its anticipated expansion in the genetic counseling market.

By End-use Insights

The biotechnology and pharmaceutical companies segment accounted for the largest market share of 52% in 2023 in genome editing market in 2023. These companies have spearheaded the development of various genome editing techniques, with a notable focus on nucleases for precise genomic alterations. While multiple technologies have advanced to clinical trials, significant challenges persist in ensuring safe, scalable manufacturing and effective drug delivery. Biotech and pharmaceutical firms continue to innovate to overcome these hurdles, aiming to bring genome editing therapies to patients efficiently and affordably. Their leadership in this sector underscores their pivotal role in shaping the future of genetic medicine.

The academic and research institutions segment is expected to grow at the fastest CAGR of 19.22% over the forecast period in the genome editing market. These institutions play a crucial role in advancing genome editing technologies across various organisms and applications. CRISPR technology, for instance, enables researchers to create disease models in animals, study genetic causes, and develop cell models using human pluripotent stem cells. Genome editing is pivotal in modifying yeast cells for biofuel production and enhancing agricultural crop strains. The expanding use of genome editing tools in academic and research settings underscores their transformative potential in advancing scientific understanding and driving innovation across multiple fields.

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Recent Developments

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Some of the prominent players in the Genome editing market include:

Key Genome Editing Companies:

The following are the leading companies in the genome editing market. These companies collectively hold the largest market share and dictate industry trends.

Segments Covered in the Report

This report forecasts revenue growth at global, regional, and country levels and provides an analysis of the latest industry trends in each of the sub-segments from 2021 to 2033. For this study, Nova one advisor, Inc. has segmented the global genome editing market.

By Technology

By Delivery Method

By Application

By Mode

By End-use

By Region

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Genome Editing Market Size to Reach USD 40.48 Billion by 2033 - BioSpace

A team of scientists created a new gene-editing tool that they claim is more accurate than the industry standard, CRISPR.

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Researchers from the University of Sydney, Australia, developed what is called SeekRNA, a new gene-editing tool that uses a programmable ribonucleic acid (RNA) strand capable of identifying and inserting itself into specific sites in genetic sequences. The team behind the project is being led by Dr. Sandro Ataide in the School of Life and Environmental Sciences, and their findings have already been published in Nature Communications.

The team explained that while CRISPR is the industry standard when it comes to genetic engineering, having revolutionized multiple industries such as medicine, agriculture, and biotechnology, it doesn't come without any problems. According to Dr. Ataide, SeekRNA differentiates itself from CRISPR in various ways, such as by not requiring any extra components to be cut and pasted into genetic sequences. SeekRNA is a stand-alone cut-and-paste tool that has higher accuracy.

Furthermore, CRISPR relies on creating a break in both strands of target DNA, which is the double-helix strand that commonly depicts a DNA sequence. While CRISPR is certainly impressive in its own right it requires the use of proteins or the DNA repair machinery to insert the new DNA sequence into its designated location. This process can produce errors in the code.

"SeekRNA can precisely cleave the target site and insert the new DNA sequence without the use of any other proteins. This allows for a much cleaner editing tool with higher accuracy and fewer errors," said Dr. Ataide

"We are tremendously excited by the potential for this technology. SeekRNA's ability to target selection with precision and flexibility sets the stage for a new era of genetic engineering, surpassing the limitations of current technologies," Dr Ataide said.

"With CRISPR you need extra components to have a 'cut-and-paste tool', whereas the promise of seekRNA is that it is a stand-alone 'cut-and-paste tool' with higher accuracy that can deliver a wide range of DNA sequences."

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Scientists create gene-editing tool that may revolutionize DNA engineering - TweakTown

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a gene-editing technology that allows scientists to modify DNA with unprecedented precision. Discovered in the early 2010s, CRISPR technology leverages a natural defense mechanism used by bacteria to protect against viral infections. The system uses a guide RNA to direct the Cas9 enzyme to a specific location in the genome, where it creates a double-strand break. This break can then be repaired by the cells natural mechanisms, allowing for the addition, deletion, or modification of genetic material. CRISPR companies are seeing more and more success in the clinic and the market is growing.

CRISPR has rapidly become one of the most powerful tools in genetic engineering, enabling precise changes to the DNA. Its applications are not limited to medicine, which will be our focus in this article, as it also allows the creation of crops with desirable traits in agriculture for instance.

In recent years, the field of CRISPR technology has improved and different forms of the technology are now being leveraged by biotech companies. Prime editing and base editing are innovative CRISPR-related technologies aiming to improve the versatility and precision of therapies.

After CRISPR Therapeutics and Vertex Pharmaceuticals collaborative success leading to CASGEVYs approval by the U.S. Food and Drug Administration (FDA) and Editas Medicines promising efforts to treat blindness, here are eight companies keeping the CRISPR field dynamic.

Beam Therapeutics was founded in 2017, and is headquartered in Cambridge, Massachusetts. The CRISPR technology company develops precision genetic medicines using its proprietary base editing technology.

The company went public on NASDAQ in February 2020 and has raised a total of $689 million since its creation according to Crunchbase.

Beams base editing technology distinguishes itself by focusing on single-base alterations, which can correct mutations at the nucleotide level. This precision reduces the risk of off-target effects and enhances the potential for treating a wide range of genetic disorders. The companys base editing platform includes the REPAIR (adenosine to inosine) and RESCUE (cytosine to uracil) systems for RNA editing, enabling targeted genetic modifications.

Beam Therapeutics has several key candidates in various stages of development:

Eligo Bioscience is a French company founded in 2014. The company focuses on precision gene editing of the microbiome to treat diseases driven by bacterial genes. Eligo Bioscience leverages its proprietary Gene Editing of the Microbiome (GEM) platform to develop therapies that target and modify specific bacterial populations. Eligo Bioscience recently raised $30 million in a series B funding led by Sanofi Ventures.

The companys GEM platform uses engineered bacteriophages to deliver CRISPR-Cas systems directly to specific bacteria within the microbiome. This approach allows for the precise elimination of pathogenic bacteria or the correction of harmful bacterial genes without disrupting the overall balance of the microbiome. By targeting bacterial genes in vivo, Eligos technology aims to address various diseases associated with microbiome dysbiosis, including antibiotic-resistant infections and chronic diseases.

Unlike broad-spectrum antibiotics, which indiscriminately kill bacteria and disrupt the microbiome, Eligos technology selectively targets pathogenic bacteria or genes within the microbiome. This precision reduces collateral damage to beneficial bacteria which helps maintain a healthy microbiome.

In January, Xavier Duportet, chief executive officer (CEO) of the company, was our guest on the Beyond Biotech podcast to talk about its flagship product EB005 targeting acne vulgaris. This candidate is on track to reach the clinic and expand its application to oncology.

Founded in 2018 and headquartered in South San Francisco, California, Epic Bio is focused on developing therapies to modulate gene expression in vivo using its proprietary Gene Expression Modulation System (GEMS) platform. The company launched in 2022 with a $55 million series A round.

Epic Bios approach combines a miniature DNA-binding protein called CasMINI with customized guide RNAs and a wide array of modulator proteins. CasMINI, licensed from Stanford University, is the smallest Cas protein to date, less than half the size of Cas9 and Cas12a, allowing for efficient delivery using adeno-associated virus (AAV) vectors. This platform enables precise gene modulation, expanding the potential for treating a variety of genetic diseases.

The CasMINI protein is engineered to function effectively in cells and is small enough to be delivered in vivo using AAV vectors. This compact size and robust functionality make it possible to target a wide range of tissues and organs with high precision.

Epic Bios pipeline is still preclinical and targets a wide variety of diseases. The companys lead candidate targets facioscapulohumeral muscular dystrophy (FSHD), a genetic muscle disorder characterized by progressive muscle weakness and wasting. The company also develops candidates for heterozygous familial hypercholesterolemia (HeFH), a genetic disorder characterized by high cholesterol levels, and retinitis pigmentosa, a group of inherited disorders that cause progressive retinal degeneration, leading to vision loss.

Locus Biosciences is a biotechnology company founded in 2015 and headquartered in Morrisville, North Carolina. The company specializes in developing precision antibacterial therapies using CRISPR-Cas3-enhanced bacteriophage technology, known as crPhage. Locus Biosciences most recent funding is a $35 million series B round in 2022.

The company employs a CRISPR-Cas3 system for its antibacterial therapies. Unlike the more commonly used Cas9, Cas3 destroys the DNA of target bacteria irreversibly, making it highly effective against antibiotic-resistant strains. This technology is delivered using engineered bacteriophages, viruses that specifically target bacteria, allowing the preservation of the microbiome.

The CRISPR-Cas3 system sets Locus apart by offering a genetic chainsaw approach, which differs from the genetic scissors approach of CRISPR-Cas9. Cas3s ability to degrade large segments of DNA makes it particularly effective for combating multi-drug resistant bacteria.

Locus lead candidate LBP-EC01 is currently in phase 2/3 and targets Escherichia coli (E. coli) infections. E. coli is a type of bacteria commonly found in the intestines of humans and animals. While most strains are harmless and part of the normal gut flora, some can cause serious infections. E. coli infections can occur through the consumption of contaminated food or water or by contact with animals or person-to-person spread.

LBP-SA01, another candidate in the companys pipeline, targets staphylococcus aureus infections. While it often exists harmlessly, it can cause a wide range of infections if it enters the body through a cut or a wound.

Founded in 2017 and headquartered in Brisbane, California, the company leverages its proprietary CRISPR platform for therapeutics and diagnostics. Like Caribou Biosciences we mentioned last week, this CRISPR company was co-founded by Nobel laureate Jennifer Doudna.

Mammoth Biosciences has raised substantial funding, including a $150 million series D financing round in 2021, which has elevated its status to a unicorn with a valuation of over $1 billion.

Mammoth Biosciences focuses on the discovery and engineering of novel CRISPR systems, specifically the ultra-small Cas14 and Cas (phi) enzymes. These systems are smaller and have an increased temperature stability, and faster reaction, which enhance their effectiveness in in vivo genome editing and diagnostics.

The use of Cas14 and Cas enzymes allows Mammoth Biosciences to develop CRISPR-based solutions that are more efficient and versatile. The smaller size of these enzymes enables easier delivery into cells, especially for diseases that affect the central nervous system.

Mammoth Biosciences is developing both therapeutic and diagnostic products. The companys therapeutic pipeline is still in the preclinical and research stages, and the indications of its candidates are mostly undisclosed.

Additionally, Mammoth has its diagnostic platform, the DETECTR platform, which is a CRISPR-based detection system.

Prime Medicine was founded in 2019 and is headquartered in Cambridge, Massachusetts. The company focuses on developing gene editing therapies using its proprietary prime editing technology. Prime editing aims to address the root causes of genetic diseases by precisely correcting mutations at their source.

The company launched with $315 million in financing, comprising a $115 million series A round followed by a $200 million series B round.

Prime Medicine utilizes prime editing, a novel gene editing technology that acts like a DNA word processor to search and replace disease-causing genetic sequences. Unlike traditional CRISPR methods, prime editing does not create double-strand breaks in DNA, which reduces the risk of unintended modifications. This technology can correct a wide range of genetic mutations, making it an interesting and promising tool for developing therapies for genetic disorders.

The technology employs a fusion protein combining a Cas protein with a reverse transcriptase enzyme and a guide RNA (pegRNA) to direct the correction process. This approach allows for highly specific and predictable edits at the targeted genomic location, minimizing off-target effects.

Prime Medicine is advancing several preclinical programs targeting various genetic diseases: Wilsons disease, preventing the body from properly eliminating excess copper and leading to severe brain and liver issues, glycogen storage disease, and retinitis pigmentosa, among others.

Primes most advanced program, however, is an ex vivo therapy in phase 1/2 targeting chronic granulomatous disease, an inherited immunodeficiency disorder that affects the bodys ability to fight certain infections.

Scribe Therapeutics is a molecular engineering company founded in 2018 and headquartered in Alameda, California. The company focuses on developing advanced CRISPR-based genetic medicines and collaborates with industry leaders such as Biogen or Sanofi.

The company recently completed a $100 million Series B financing round led by Avoro Ventures and Avoro Capital Advisors.

Scribe Therapeutics leverages its CRISPR by design platform, which includes custom-engineered CRISPR enzymes. By optimizing the CRISPR enzymes for greater efficiency, Scribes XE technology can achieve more precise and robust gene edits.Scribes XE platform features advancements in delivery technologies, such as viral vectors and lipid nanoparticles, that are optimized for delivering CRISPR components into target cells and tissues in vivo.

The CRISPR company works on several therapeutic areas hand in hand with key players in the industry. Scribe is collaborating with Biogen to develop CRISPR-based therapies for amyotrophic lateral sclerosis (ALS). In partnership with Sanofi, Scribe is also working on genetically modifying natural killer (NK) cell therapies for cancer treatment. The XE platforms high specificity and efficacy make it ideal for engineering these cells to target and eliminate cancer cells effectively.

SNIPR Biome was founded in 2017 and is headquartered in Copenhagen, Denmark. The company specializes in developing CRISPR-based microbial gene therapies aimed at precisely targeting and eradicating pathogenic bacteria, including antibiotic-resistant strains.

SNIPR Biome has raised notable funding including one of Europes largest series A rounds, securing $50 million.

SNIPR Biomes primary technology involves CRISPR-Guided Vectors (CGV), which deliver CRISPR components into bacterial cells via engineered bacteriophages. These vectors create double-stranded breaks in the DNA of target bacteria, leading to rapid and specific bacterial killing. This approach is designed to preserve beneficial microbiota while targeting harmful pathogens, particularly those resistant to conventional antibiotics.

SNIPR001 is the companys lead candidate, a CRISPR therapy targeting E. coli, including antibiotic-resistant strains. SNIPR001 is designed to prevent bloodstream infections in patients undergoing hematopoietic stem cell transplants, who are particularly vulnerable to such infections. Positive interim results from phase 1 clinical trials showed that SNIPR001 was well-tolerated and effectively reduced gut E. coli levels in treated individuals.

The CRISPR technology market is experiencing robust growth and substantial investments. In 2024, the global market was valued at approximately $3.78 billion and is projected to reach around $9.34 billion by 2029, growing at a compound annual growth rate (CAGR) of 19.9%. This promising outlook for the CRISPR market is driven not only by the recent success of companies like Vertex and CRISPR Therapeutics but also by the emergence of more refined versions of the CRISPR technology.

While there is no doubt CRISPR has a bright future ahead, the market faces several challenges. The high costs associated with CRISPR technology are one of the main obstacles to its democratization in the future. Ethical concerns regarding genetic modifications and regulatory hurdles are also significant obstacles as ethics and law always move slower than technology.

More broadly, the gene editing and engineering scenes are moving fast, and technologies such as epigenetic editing and gene writing with companies such as Chroma Medicine and Tessera Therapeutics show significant potential.

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This two-part review provides high-level analytical development considerations for exvivo, genome-modified hematopoietic stem and progenitor cell (GM-HSPC) products derived from primary donor cells. Part 1 in BPIs May 2024 issue addresses analytical controls for in-process drug substances and drug products. Here in Part 2, we take a step back to examine concerns for HSPC source materials. Look to other recently published reviews for a broader discussion of chemistry, manufacturing, and controls (CMC) for GM-HSPCs (19, 20) and for development considerations with gene-edited pluripotent stem cells (PSCs) (21). Note that we use the term genome modified in a generic sense herein to include products that are manufactured by means of viral-vector transduction (typically by lentiviral vectors (LVVs)) and those subject to genome editing by such means as a system based on clustered regularly interspaced palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9).

Analytical Controls for Starting Materials and Drug Substances

To ensure GM-HSPC quality, thorough analytical control strategies should be implemented that include a phase-appropriate set of in-process, characterization, and release tests to monitor both manufacturing processes and drug products. Figure 2 depicts a generic GM-HSPC manufacturing process, beginning with the introduction of cellular starting material, which is controlled through establishment of donor eligibility criteria and starting-material testing. Genome-modification reagents e.g., nucleases, single-guide RNA (sgRNA), and viral vectors usually are classified as drug substances and thus are subject to release testing before their entry into the manufacturing process. Control of both cellular starting material and genome-modification reagents are discussed below. Note that GM-HSPC manufacturing processes often proceed uninterrupted, and often there is minimal or no testing of cellular drug substances.

Figure 2: Standard manufacturing process for genome-modified hematopoietic stem and progenitor cell (GM-HSPC) therapies. sgRNA = single-guide ribonucleic acid.

Many starting materials and critical reagents for products such as GM-HSPCs can be of varying quality and/or the product of bespoke manufacturing, themselves. Thus, it is necessary to place significant emphasis on the analysis of cellular starting materials and genome-modification reagents. For these complex products, investing up front in a comprehensive analytical approach might help to accelerate development and mitigate later-stage risks.

Cellular Starting Materials: Most GM-HSPC processes including those used to make the six commercially approved products to date (see Part 1, Table 1) rely on the acquisition of autologous cellular starting material (6671). Allogeneic products have entered clinical development recently (72). Such efforts include ongoing work to establish universal HSPCs derived from PSCs. Those products are beyond the scope of this review; considerations for their development were described by Morse and Mack in 2023 (21).

Whether derived from an autologous or allogeneic source, control of cellular starting material follows two parallel pathways: donor eligibility determination and cellular testing (Table 3). Questionnaires, medical examinations, and viral testing serve to establish donor eligibility (73, 74). Donor testing typically includes testing for hepatitis, human immunodeficiency virus (HIV), and other pathogens as well as prion contagions. After those screenings, eligible donors are subjected to a mobilization regimen that enables CD34+ stem cells to move from the donors bone marrow to their peripheral blood (75, 76). Thus mobilized, they provide peripheral-blood donation that is subjected to leukapheresis, extraction of white blood cells from the peripheral blood (9). Alternatively, CD34+ stem cells may be acquired by extraction of bone marrow directly from the hip bone (9).

Table 3: Control of cellular starting materials includes both assessment of donor eligibility and testing of those materials. Minimal donor eligibility considerations are provided below; for a more extensive discussion, see reference 74. Abbreviations: CJD = CreutzfeldtJakob disease; HIV = human immunodeficiency virus; HTLV = human T-lymphotropic virus; HBV = hepatitis B virus; HCV = hepatitis C virus; TSE = transmissible spongiform encephalopathy; WNV = West Nile virus.

Cellular testing begins upon receipt of leukopaks or other starting material at the biomanufacturing site. Such testing typically focuses on the quantity and health of target CD34+ cells through testing of viability and measurement of both total nucleated cell count and the percentage of CD34+ cells present. When possible, limits for such tests should be based on manufacturing capability and potential effects on critical quality attributes (CQAs). Limits are likely to be established based on a minimum viability to provide a product of sufficient quality and a minimal cell count and CD34+ percentage to ensure adequate dosing. Additional tests e.g., safety testing or analysis of specific cell phenotypes also might be considered necessary for a GM-HSPC program.

Precedents have been established for several approaches to genetic modification of HSPCs (77). For our purposes, we consider genome-modification reagents including viral vectors, nucleases, and sgRNA to be active pharmaceutical ingredients (APIs) or drug substances and therefore subject to an appropriate level of analytical control (78). Release of each reagent should be contingent upon demonstration of sufficient purity, safety, and potency.

Nucleases: Release specifications for nucleases such as the Cas9 protein should be set to ensure both the consistency of the manufactured nuclease and the safety, purity, and potency of the corresponding GM-HSPC drug product. Table 4 lists typical assays for nuclease release. The list is not exhaustive and applies only to the given nuclease (protein) itself, although similar principles apply to mRNA as well.

Table 4: Typical assays included in a nuclease-release assay panel. Abbreviations: ELISA = enzyme-linked immunosorbent assay; HPLC = high-performance liquid chromatography; qPCR = quantitative polymerase chain reaction; SEC = size-exclusion chromatography; USP = United States Pharmacopeia.

Perhaps the most important nuclease attributes are safety and activity, which are key to ensuring quality of GM-HSPC drug products. Safety test panels include compendial sterility, mycoplasma, and endotoxin assays (or equivalents); activity assays might be designed to measure the ability of a nuclease to cut (or otherwise modify) template DNA. Evaluation of purity typically requires a method such as high-performance liquid chromatography (HPLC) to measure the percentage of intact, full-length nuclease molecules. Impurity determination often relies on multiple assays to evaluate host-cell proteins (HCPs), host-cell DNA, and nuclease degradants/aggregates present in a product sample.

An increasing number of good manufacturing practice (GMP)quality nucleases have become available commercially, providing a useful route to minimizing cost and complexity relative to internal manufacturing (7981). However, to ensure that suppliers can support GM-HSPC programs throughout development, product sponsors should exercise appropriate oversight (e.g., vendor management programs, audits, and so on) before integrating off-the-shelf options. For early stage clinical development, that includes robust platform assays and specifications that are appropriate for manufacturing HSPC drug products. For later-stage development including studies enabling licensure of clinical material and commercial manufacturing sponsors should ensure that their suppliers have strong analytical validation programs in place. In such later phases, sponsors also need their own appropriate quality systems and risk-assessment procedures with associated documentation of all changes in production processes and analytical methods.

Single-Guide RNA: Given the critical nature of sgRNA sequences in determining CRISPR/Cas9 specificity, their purity and identity are considered to be critically important to PQAs. Ion-pair reversed-phase HPLC (IP-RP HPLC), which separates oligonucleotides based on their length and charge, is a standard method used for measuring sgRNA purity (81). Note, however, that both molecular length and commonly used chemical modifications such as phosphorothioate linkages can present significant challenges in the use of chromatographic approaches (82). Mass-spectrometry (MS) and next-generation sequencing (NGS) approaches also can be used for establishing sequence purity.

Recent publications demonstrate that LC-MS approaches can be used to demonstrate sequence identity, to detect sequence modifications, and possibly to establish the sequence purity of targeted regions of sgRNA molecules (8385). However, LC-MS has yet to sequence full-length sgRNA quantitatively. NGS analysis theoretically should apply to quantitative sequencing of sgRNA but for evaluation of chemical modifications, although biases during amplification can complicate the techniques reliability in quantitating sequences (86). Such effects should be evaluated before implementation of NGS assays for sgRNA purity assessment. Table 5 lists assays usually found on sgRNA release-testing panels.

Table 5: Typical assays included in a release-assay panel for sgRNA. Abbreviations: GC = gas chromatography; IP-RP HPLC = ion-pair reversed-phase high-performance liquid chromatography; LC-MS = liquid chromatographymass spectrometry; NGS = next-generation sequencing; ICP-MS = inductively coupled plasma mass spectrometry; sgRNA = singleguide ribonucleic acid; USP = United States Pharmacopeia.

Ribonucleoprotein (RNP): Neither sgRNA nor RNA-directed nucleases have significant biological activity in isolation. Rather, those components combine to form RNP complexes that modify DNA. Thus, regulators expect sponsors to provide at least some characterization of those complexes. For cases in which RNPs are prepared ex vivo, sponsors at minimum should implement both purity and activity assays to characterize those complexes. Purity assessments may include analysis of both the proportion of intact RNP and proportions of sgRNA and nuclease present (87); activity assays probably can be established in the same manner as noted above for the release of sgRNA or nuclease.

Viral Vectors: Lentiviral vector (LVV) manufacturing poses several challenges, including needs for consistent production (e.g., by stable and high-yielding producer cell lines) and for highly accurate titer assays for quantifying LVV concentrations and safety (8889). Unlike other viral vectors, LVV production poses difficulty to those companies attempting to use stable cell lines (90). Thus, most conventional practices use transient transfection of adherent cell lines, which has presented difficulties in scale-up (91). That said, establishing stable cell lines would eliminate steps required for transient transfection and enable continuous and consistent vector production (92).

Analytical control of LVVs involves a comprehensive and well-established set of methods and techniques for ensuring the quality, purity, and functionality of vector preparations. Several methods are used in quantifying viral titers to ensure the appropriate dosage for intended applications. Those methods can be categorized broadly into functional and nonfunctional approaches (93). Nonfunctional (physical) titer methods include assessments of p24 capsid protein and lentiviral RNA levels. A significant disadvantage of such methods is the potential for overestimating vector titers through quantification of protein or RNA coming from both functional and defective vector particles (93). Infectious titer assays use real-time quantitative polymerase chain reaction (RT-qPCR) to measure mRNA expression from transduced cells. Such a functional approach is considered to be more accurate for determination of functional titers (94).

Additional key aspects of analytical control include evaluating the absence of contaminants such as HCPs, nucleic acids, and other foreign particles; verification that LVVs have the correct genetic material and maintain their intended identity; assessment of the vectors ability to achieve desired transduction efficiency; and analysis of LVV integration patterns within a host genome to evaluate the risk of insertional mutagenesis (95). Table 6 is a typical release-testing panel for LVVs used in manufacturing GM-HSPCs.

Table 6: Standard viral vector release-assay panel. * In this context, dose-defining refers to the dose used in the manufacturing process. ** Residual impurities can include residual plasmid DNA (pDNA), host-cell proteins, host-cell DNA (potentially including E1A and SV40 DNA sequences), and encapsulated residual DNA (potentially including plasmids, host-cell DNA, E1A). Abbreviations: CE-SDS = capillary electrophoresissodium dodecyl sulfate; DLS = dynamic light scattering; ELISA = enzyme-linked immunosorbent assay; GM-HSPC = genetically modified hematopoetic stem and progenitor cells; LVV = lentiviral vector; qPCR = quantitative polymerase chain reaction; SDS-PAGE = sodium dodecyl sulfatepolyacrylamide gel electrophoresis; USP = United States Pharmacopeia.

With measures such as splitting of the LVV genome into separate plasmids and partial deletion of the 3' long-terminal repeat (LTR) reducing risks of replication competence, the safety of LVVs has improved over the years, thus minimizing the associated patient safety risks (96). The recommended assay for assessing replication-competency of viruses involves coculture with indicator cells and subsequent evaluation of the presence of viral protein and/or DNA sequences. Nevertheless, alternative rapid methods can be used for detecting replication-competent LVV if their equivalence or superiority to the traditional coculture assay can be demonstrated (97).

Rising to the Challenges

Whether manufactured through viral-vectormediated gene delivery, nuclease-mediated editing, or both, genome modification of HSPCs represents a significant advancement in the potential to cure diseases that otherwise have suboptimal or no currently available treatment options. Building on a substantial therapeutic legacy of HSC transplants, these new therapies are complex to manufacture and require broad and deep analytical support to ensure adequate and consistent product quality (13).

GM-HSPCs face two key analytical challenges: First, the components used to manufacture them are often bespoke and require significant analytical oversight. Second, as detailed in Part 1 of this review, the broad range of materials used to manufacture a GM-HSPC can include proteins, nucleic acids, viral vectors, and cellular materials. Each of those requires the development of its own bespoke analytical approach, including specific analytical tools and methods. Challenges associated with appropriate characterization of GM-HSPC products will increase as the field matures, with the potential addition of new gene-editing techniques such as base and Prime editing and gene writing (6264) as well as in vivo targeting approaches (65).

Thus, GM-HSPC sponsors are advised to put significant thought into the development of appropriate analytical control strategies for each of their candidate therapies. Doing so can help maximize the probability of regulatory, technical, clinical, and commercial success, thus helping to maximize the likelihood of each candidate achieving its therapeutic potential.

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Corresponding author Brent Morse is a principal consultant, and Alicja Fiedorowicz is an analytical consultant in cell and gene therapy, both at Dark Horse Consulting Group near Boston, MA; [emailprotected].

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