Genome editing technologies such as the CRISPR-Cas9 system allow for precise changes to the DNA code. These technologies have the potential to cure some of the most severe human diseases by precisely correcting genes within a patient’s own body. However, much more work is needed to establish which somatic genome editing systems will be efficient and safe enough for use in humans. As part of a larger effort of the National Institutes of Health’s Somatic Cell Genome Editing (SCGE) program, researchers at Baylor College of Medicine and Rice University have been awarded a U42 grant to create mouse model resources for testing the therapeutic potential of novel genome editing approaches. The project, which provides $2 million in funding over five years, is titled “BCM-Rice resource for the analysis of somatic gene editing in mice.”

The SCGE program was initially launched by the NIH to address key barriers to progress in somatic genome editing, including the development of delivery systems and novel editing enzymes. Associated grants will support four goals: to develop new delivery and editing systems, to develop cell and tissue platforms to assess adverse consequences of genome editing, to develop mouse or rat strains in which genome editing activity can be reported, and to develop large-animal models for testing.

“If successful, the SCGE program will accelerate the translation of genome editing technologies into treatments for human diseases,” said Dr. Jason Heaney, assistant professor of molecular and human genetics at Baylor and principal investigator on the U42 grant.

One of the major aims of the Baylor-Rice project is to develop reporter animals, in this case mice, to allow for quantitative evaluation of both targeted and undesired genome editing events in individual cell types. In the second phase of the project, the group will evaluate the efficacy and safety of genome editing delivery systems and novel editing enzymes developed by other members of the SCGE program. The team will also make the new reporter mice available for distribution to the broader scientific community.

“The long-term goal of our project is to accelerate the clinical development of somatic genome editing for human disease by defining the benefits and risks of novel delivery technologies and editing enzymes,” said Dr. Mary E. Dickinson, principal investigator on the grant and professor and Kyle and Josephine Morrow Chair in the Department of Molecular Physiology and Biophysics. “This project builds on already existing strengths at Baylor and Rice in mouse model research and genome editing technologies.”

Dr. Bill Lagor, principal investigator on the project and assistant professor of molecular physiology and biophysics at Baylor, added, “We are very excited about having the opportunity to serve as a testing center for delivery systems as well as new genome editing tools. This is an important resource that will allow us to determine the efficiency and safety of these approaches in live organisms. We believe this resource will fill an important gap in the preclinical pipeline for tissue-directed genome editing reagents intended for eventual therapeutic use.”

The project is a collaborative effort between Baylor and Rice. The multi-principal investigator team consists of Heaney, Lagor and Dickinson. Co-investigators on the project include Drs. John Seavitt and Karl-Dimiter Bissig with Baylor, and Gang Bao with Rice University.