Photo: An illustration depicts a genome editing tool bound to a DNA helix. New genome editing tools can substitute single “letters” in the DNA code without changing the surrounding DNA structure. (Credit: XVIVO Photo)
Somatic Cell Genome Editing support is aimed at improving therapeutic options for both rare and common diseases
Making changes to a patient's DNA can have powerful implications for the treatment of disease. To tap into this immense potential, the National Institutes of Health (NIH) recently awarded 21 Somatic Cell Genome Editing grants — totaling approximately $86 million over the next five years, pending available funds — to support research aimed at improving methods to edit the human genome. These grants are the first to be awarded through the Somatic Cell Genome Editing (SCGE) program, which was launched in January 2018 with NIH Common Fund support. As a trans-NIH endeavor, SCGE is managed by staff from multiple NIH institutes and centers, with leadership from the National Center for Advancing Translational Sciences (NCATS).
A genome is an individual’s complete set of DNA, the chemicals that carry genetic information. Many diseases are caused by DNA changes that can be inherited from parents or can happen during a person’s lifetime. In the past decade, scientists have developed techniques to edit DNA in living cells. The newly awarded grants focus on somatic cells, which are cells in the body other than reproductive — e.g. sperm and egg — cells. One concern about manipulating genetic material has been the possibility of passing on unintended and potentially harmful genetic mutations. But because somatic cells do not pass DNA to the next generation, genome editing changes in somatic cells cannot be inherited.
“Human genome editing technologies have opened up many far-reaching possibilities to treat disease,” says NCATS Director Christopher Austin, MD. “The intent is that these newly funded initiatives will help speed the translation of genome editing to the clinic and to a greater number of patients with what are currently intractable illnesses and conditions.”
Learn more about the SCGE program and its goals
Researchers continue to make improvements in genome editing techniques and understanding their effects, but significant barriers remain before they will be used widely to treat patients.
“One challenge is to deliver genome editing tools to the right cells at the right time,” says P.J. Brooks, PhD, program director, NCATS Office of Rare Diseases Research. “With these awards, research teams will collaborate on several projects to improve the delivery of these tools to disease-relevant cells in the lung, muscle, brain, and other tissues.”
Aravind Asokan, PhD, Professor of Surgery and Director of Gene Therapy, has been awarded a grant for his project "Evolving high-potency adeno-associated virus (AAV) vectors for neuromuscular genome editing." Recombinant adeno-associated viruses (AAVs) have emerged as safe and effective vectors for clinical gene therapy applications, including systemic treatment of neuromuscular diseases, such as spinal muscular atrophy, Duchenne muscular dystrophy, and giant axonal neuropathy. However, genome editing in neuromuscular tissue is challenging. Dr. Asokan's project will develop a comprehensive and innovative approach to evolve high-potency AAV variants for systemic neuromuscular genome editing.
The awards will also support:
- New and more effective genome editing tools
- Methods to evaluate the safety and effectiveness of various genome editing techniques in different human cell types
- Specific animal models in which to test genome editing tools and methods
- Testing centers to validate findings to ensure research results can be reproduced
- Development of a genome editing toolkit — including lessons learned, and new techniques and tools — to be broadly disseminated to the scientific community
“Common Fund programs can boost a developing area of biomedical research but don’t focus on a specific organ system or disease,” says James M. Anderson, MD, PhD, director of the Division of Program Coordination, Planning, and Strategic Initiatives, which oversees the NIH Common Fund. “If we can improve the safety and effectiveness of genome editing, we have the potential to treat a wide variety of diseases or conditions.”
The broad applicability of genome editing to biomedical research is reflected in the diversity of NIH institutes and centers involved in the SCGE program. In addition to NCATS, the NIH’s National Heart, Lung, and Blood Institute, National Institute of Allergy and Infectious Diseases, National Institute of Neurological Disorders and Stroke, National Institute of Arthritis and Musculoskeletal and Skin Diseases, and Office of Research Infrastructure Programs are managing these awards. The program will award researchers a total of approximately $190 million over six years, pending the availability of funds.
For more information, visit https://ncats.nih.gov/somatic and https://commonfund.nih.gov/editing.
For a list of the grantees and information about their awards, see: https://commonfund.nih.gov/editing/fundedresearch.