NYSCF Innovator Improves CRISPR Genome Repair

CRISPR is a revolutionary gene-editing technology that has many potential applications in medicine. Derrick Rossi, PhD, Associate Professor at Harvard University and NYSCF – Robertson Investigator Alumnus, recently published a paper in Nature Biomedical Engineering where he has improved upon the process of CRISPR-mediated genome editing. Improving the efficiency and securing the accuracy of CRISPR tools will enable gene editing to jump from the laboratory to clinical use in patients.

After a part of the genome is disrupted, it must be repaired, and scientists are aiming to control this repair mechanism in the most accurate and efficient manner possible. Currently, there are two pathways that are utilized for targeted CRISPR genome repair: non-homologous end-joining (NHEJ) and homology-directed repair (HDR). The former tends to be highly efficient, but can be error-prone and the process can result in incorrect changes to the genome. HDR is precise, but occurs at a lower frequency than NHEJ in mammalian cells, creating a bottleneck that limits the process in precision genome editing.

Dr. Rossi has shown that with the expression of RAD52, a protein not usually expressed in HDR, and dn53BP1, an altered form of 53PB1 (regularly found in the NHEJ pathway), he was able to enable efficient HDR at multiple points of the genome in patient-derived induced pluripotent stem cells. Co-expression of these two proteins improved efficiency, maintained the accuracy of HDR, and did not alter any activity in positions not targeted by CRISPR.

Read the paper in Nature Biomedical Engineering

Diseases & Conditions:

Genomics & Gene Editing

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