Suppression of NF1 Nonsense Mutations by RNA-guided RNA Pseudouridylation

A significant proportion (≈20%) of NF1 mutations generate a premature “stop” signal in the middle of the NF1 gene, leading to a truncated and non-functional NF1 protein. To correct these mutations, we propose developing a novel approach, namely RNA-guided RNA modification, to fix the mistakes at the mRNA level by converting the premature “stop” signal back into a “go” signal. We have successfully tested this approach in therapeutically relevant genes in several human cell lines. With the support of the Gilbert Family Foundation research grant, we will go one step further to test our approach directly in Neurofibromatosis Type 1 patient-derived cells carrying a premature “stop” signal in the NF1 gene. We believe we will succeed in developing a new RNA therapy to treat NF1 via restoration of functional neurofibromin in the cells to stop or even reverse the course of the disease.

Investigators

Yi-Tao Yu, PhD

University of Rochester

Yi-Tao Yu, PhD

University of Rochester

Current Stage

Discovery

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