Somatic Cell Genome Editing Highlights

A team approach to help reduce the burden of genetic diseases

Somatic Cell Genome Editing ConsortiumMaking changes to a patient’s DNA can have powerful implications for the treatment of disease. Over the past decade, a steady progression of genome editing techniques and technologies has made it possible to precisely change the DNA inside living cells. 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. Specifically, editing cells inside the human body still faces significant hurdles in achieving efficacy and safety. Getting genome editing tools into the various cells of the body will require the development of genome editing approaches specialized to the target cell type and location within the body. The NIH Common Fund launched the Somatic Cell Genome Editing (SCGE) Program in 2018 by assembling a collection of multidisciplinary teams working on individual projects designed to develop solutions to these challenges collectively.

A marker paper written by the SCGE consortium of researchers outlines the goals and strategies of the consortium, which now includes 72 principal investigators from 38 institutions pursuing 45 distinct but well-integrated projects. The goal of the SCGE consortium is to improve the efficacy and specificity of genome editing approaches to reduce the burden of disease. It is accomplishing this goal through components that are working together to develop and improve editing and delivery tools that target specific genes and tissues. They are also collaborating to conduct safety and efficacy tests of these tools via new methods, platforms, and animal models. Information on these tools and other resources will be delivered in an on-line toolkit for therapeutic genome editing that will enable biomedical researchers to more rapidly develop therapies for a variety of genetic disorders.

Reference:
The NIH Somatic Cell Genome Editing Program. Krishanu Saha, Erik J. Sontheimer, P.J. Brooks, Melinda R. Dwinell, Charles A. Gersbach, David R. Liu, Stephen A. Murray, Shengdar Q. Tsai, Ross C. Wilson, Daniel G. Anderson, Aravind Asokan, Jillian F. Banfield, Krystof S. Bankiewicz, Gang Bao, Jeff W. M. Bulte, Nenad Bursac, Jarryd Campbell, Daniel F. Carlson, Elliot L. Chaikof, Zheng-Yi Chen, R. Holland Cheng, Karl J. Clark, David T. Curiel, James E. Dahlman, Benjamin E. Deverman, Mary E. Dickinson, Jennifer A. Doudna, Stephen C. Ekker, Marina E. Emborg, Guoping Feng, Benjamin S. Freedman, David M. Gamm, Guangping Gao, Ionita C. Ghiran, Peter M. Glazer, Shaoqin Gong, Jason D. Heaney, Jon D. Hennebold, John T. Hinson, Anastasia Khvorova, Samira Kiani, William R. Lagor, Kit S. Lam, Kam W. Leong, Jon E. Levine, Jennifer A. Lewis, Cathleen M. Lutz, Danith H. Ly, Samantha Maragh, Paul B. McCray, Jr., Todd C. McDevitt, Oleg Mirochnitchenko, Ryuji Morizane, Niren Murthy, Randall S. Prather, John A. Ronald, Subhojit Roy, Sushmita Roy, Venkata Sabbisetti, W. Mark Saltzman, Philip J. Santangelo, David J. Segal, Mary Shimoyama, Melissa C. Skala, Alice F. Tarantal, John C. Tilton, George A. Truskey, Moriel Vandsburger, Jonathan K. Watts, Kevin D. Wells, Scot A. Wolfe, Qiaobing Xu, Wen Xue, Guohua Yi, Jiangbing Zhou and rest of the SCGE Consortium. Nature, 2021 April 7.

 

markerpaper

A genome editing tool increases lifespan in diseased mice

Many common and rare diseases are caused by harmful changes in DNA. Hutchinson-Gilford progeria syndrome (HGPS) is a rare disease that is caused by a DNA change that induces rapid aging and shortens lifespan. While millions of Americans live with rare diseases like HGPS, most have no treatment options available. Recent scientific advances in correcting harmful DNA changes have made it possible to treat and even cure some genetic diseases. However, one significant remaining challenge is to design different types of DNA editing tools to correct different types of harmful DNA changes. The NIH Common Fund’s Somatic Cell Genome Editing (SCGE) program is working to improve the efficacy and specificity of genome editing approaches to reduce the burden of disease caused by genetic changes.

In a groundbreaking study, NIH Director Dr. Francis Collins, and SCGE researcher Dr. David Liu, with their colleagues, used a genome editing tool that specifically targeted and corrected the disease-causing gene both in cells obtained from HGPS patients and in a mouse model of HGPS. The delivery of this tool into lab-grown cells from HGPS patients resulted in 90% of the cells containing the edited gene and a significant reduction in cellular abnormalities. A single use of the tool in the mouse model greatly extended lifespan from 215 to 510 days. Improved health in the aorta was also observed in the hearts of treated mice, which was particularly encouraging because deterioration of the aorta is a major contributor to disease and death in children with HGPS. Overall, these findings support the potential for genome editing tools to treat HGPS, and other genetic diseases, by directly correcting the root cause of disease.

Reference:
In Vivo Base Editing Rescues Hutchinson-Gilford Progeria Syndrome in Mice. Luke W. Koblan, Michael R. Erdos, Christopher Wilson, Wayne A. Cabral, Jonathan M. Levy, Zheng-Mei Xiong, Urraca L. Tavarez, Lindsay Davison, Yantenew G. Gete, Xiaojing Mao, Gregory A. Newby, Sean P. Doherty, Narisu Narisu, Quanhu Sheng, Chad Krilow, Charles Y. Lin, Leslie B. Gordon, Kan Cao, Francis S. Collins, Jonathan D. Brown, David R. Liu. Nature, 2021 January 6.

In the news:
DNA-editing method shows promise to treat mouse model of progeria

Watch the scientists describe their work and its impact:

progeria

This page last reviewed on April 7, 2021