Title: Tools for editing the genomes of cells within the body
Legend: Activities of the SCGE Consortium converge on editing the genome of cells inside the human body. A. Targets of the genome editors (right) range from DNA within the nucleus of a cell to other nucleic acids elsewhere within a cell, such as DNA within the mitochondria (mtDNA) or RNA in the cytoplasm. Targets of epigenomic editors (left) produce targeted alteration of the chromatin structure—including remodelling, modification of the 3D structure and the direct modification of histones or DNA—without editing the DNA or RNA sequence. Approaches to editing cells outside of the body, as well as germline editing in embryos, are not directly supported by the SCGE Consortium, nor are strategies for gene augmentation through the addition of exogenous DNA. B. Interoperable tools assembled into an SCGE Toolkit will be disseminated to accelerate the translation of safe and effective genome-editing therapeutics into the clinic. Tools encompass several categories shown on the right: newly developed genome editors, delivery technologies, reporter-animal systems, and human biological systems.
Citation: Saha, K., Sontheimer, E. J., Brooks, P. J., Dwinell, M. R., Gersbach, C. A., Liu, D. R., Murray, S. A., Tsai, S. Q., Wilson, R. C., Anderson, D. G., Asokan, A., Banfield, J. F., Bankiewicz, K. S., Bao, G., Bulte, J. W. M., Bursac, N., Campbell, J. M., Carlson, D. F., Chaikof, E. L., … SCGE Consortium. (2021). The NIH Somatic Cell Genome Editing program. Nature, 592(7853), 195–204. https://doi.org/10.1038/s41586-021-03191-1
Abstract: The move from reading to writing the human genome offers new opportunities to improve human health. The United States National Institutes of Health (NIH) Somatic Cell Genome Editing (SCGE) Consortium aims to accelerate the development of safer and more effective methods to edit the genomes of disease-relevant somatic cells in patients, even in tissues that are difficult to reach. Here we discuss the consortium’s plans to develop and benchmark approaches to induce and measure genome modifications, and to define downstream functional consequences of genome editing within human cells. Central to this effort is a rigorous and innovative approach that requires validation of the technology through third-party testing in small and large animals. New genome editors, delivery technologies and methods for tracking edited cells in vivo, as well as newly developed animal models and human biological systems, will be assembled—along with validated datasets—into an SCGE Toolkit, which will be disseminated widely to the biomedical research community. We visualize this toolkit—and the knowledge generated by its applications—as a means to accelerate the clinical development of new therapies for a wide range of conditions.
About the Lab: The Saha Lab is affiliated with several multi-disciplinary centers including the Waisman Center, Wisconsin Institute for Discovery and the Stem Cell and Regenerative Medicine Center at UW-Madison. Our research dedicated to using human stem cells together with emerging engineering methods in material science and synthetic biology to make smarter therapeutics, model human disease, and advance personalized medicine. We are collaborative efforts on campus in biomanufacturing cell and gene therapies, and nationally with the NIH Somatic Cell Genome Editing program and the NSF Center for Cell Manufacturing Technologies.