Optimization of Base and Prime Editing Strategies for NF1 Therapeutics

Recent advances in CRISPR-based gene editing strategies may offer lifelong restoration of neurofibromin deficiency by permanent correction of NF1 mutations. In this project, we plan to develop safe and effective genome editing strategies to treat NF1 tumors. Lymphoblastoid cell lines derived from blood will provide a patient-specific resource to facilitate optimization of gene editing strategies, allowing candidate designs to be tested for both on-target efficacy of gene correction and fidelity. In parallel we will continue our efforts to develop novel engineered Cas variants that overcome limitations of naturally occurring enzymes to improve tile efficiency and precision of BEs and PEs. Preclinical testing of promising editing strategies will be conducted both in Schwann cells derived from induced pluripotent stem cells and in patient-derived tumor xenografts (POX) in mice.

Investigators

James Walker, PhD

Massachusetts General Hospital

Benjamin Kleinstiver, PhD

Massachusetts General Hospital

Angela Hirbe, MD, PhD

Washington University in St. Louis

James Walker, PhD

Massachusetts General Hospital

Benjamin Kleinstiver, PhD

Massachusetts General Hospital

Angela Hirbe, MD, PhD

Washington University in St. Louis

Current Stage

Discovery

Discovery
In Vivo Proof of Concept
IND Enabling
Clinical Trial Phase 1
Clinical Trial Phase 2
Clinical Trial Phase 3