Somatic Cell Genome Editing
Scientists use CRISPR-Cas9 gene editing technology to selectively modify the DNA of living organisms.
The broad applicability of targeted and programmable genome editing approaches, including those based on CRISPR-Cas9, raise the potential of new ways to treat a variety of rare genetic diseases, as well as common diseases. However, many challenges need to be overcome before such techniques can be widely used in the clinic. ORIP manages an Animal Models Initiative as a component of the recent NIH Common Fund Phase 1 Somatic Cell Genome Editing (SCGE) Program. This initiative focuses on creating better animal models for assessing genome editing in vivo and has already produced and validated state-of-the-art rodent and pig reporter strains to allow detection of on-target and off-target genome editing in individual cells.
Building upon the success of the Animal Models Initiative and to assist in facilitating SCGE Phase 2, ORIP is funding four projects through the new Testing Centers for Development of SCGE in Model Organisms (PAR-23-038). These Centers specialize in major mammalian animal model species (rodents, pigs, and nonhuman primates) and are designed to develop new genome editing technologies, conduct preclinical testing of therapeutics to treat human diseases, and provide resources and testing services to a growing biomedical community. The Testing Centers are also assisting NIH-funded investigators in assessing the efficacy and safety of in vivo genome editing and delivery technologies, determining genome editing thresholds for specific diseases associated with minimal off-target effects, and ascertaining feasibility parameters in a model system.
Examples of projects funded by ORIP:
Center for Somatic Cell Genome Editing in Nonhuman Primates
U42OD035737
Dennis J. Hartigan-O’Connor, David J. Segal, Alice F. Tarantal (contact)
University of California, Davis
https://csge.ucdavis.edu
Swine Somatic Cell Gene Editing Testing Center
U42OD035738
Jonathan A. Green, Kevin Dale Wells (contact)
University of Missouri
https://nstc.missouri.edu/
BCM/Rice Genome Editing Testing Center
U42OD035581
Jason D. Heaney (contact), William Raymond Lagor, Christopher John Walkey
Baylor College of Medicine
https://www.bcm.edu/research/research-centers/baylor-rice-genome-editing-testing-center
MU Rodent Testing Center for Somatic Cell Genome Editing
U42OD035739
Elizabeth C. Bryda
University of Missouri
https://www.rrrc.us
Recent Selected Grantee Publications
Liver-Specific Transgenic Expression of Human NTCP In Rhesus Macaques Confers HBV Susceptibility on Primary Hepatocytes
Rust et al., PNAS. 2025.
This study establishes the first transgenic nonhuman primate model for hepatitis B virus (HBV). Male and female rhesus macaques were engineered to express the human HBV receptor, NTCP (hNTCP),…
Preclinical Use of a Clinically-Relevant scAAV9/SUMF1 Vector for the Treatment of Multiple Sulfatase Deficiency
Presa et al., Communications Medicine. 2025.
This study evaluates a gene therapy strategy using an adeno-associated virus (AAV)/SUMF1 vector to treat multiple sulfatase deficiency (MSD), a rare and fatal lysosomal storage disorder caused by…
A Comprehensive Atlas of AAV Tropism in the Mouse
Walkey et al., Molecular Therapy. 2025.
Over the past three decades, adeno-associated viruses (AAVs) have emerged as the leading viral vector for in vivo gene therapy. This study presents a comprehensive atlas of AAV tropism in male and…