DUX4 mRNA silencing using RNA editing by CRISPR-Cas13-ADAR2 and endogenous ADAR

Investigator: Scott Q Harper PhD

Category: Research - Translational

After many years of research, we now know that FSHD is caused by the toxic DUX4 gene being turned on in muscle cells. Discovery of the DUX4 disease gene provided an important target for developing FSHD therapies. These therapies aim to stop the DUX4 gene from being made and help reduce the damage it causes in muscle. In this proposal, we aim to develop a new approach for treating FSHD by using a cutting-edge technique called RNA editing. When a gene is turned on, it produces a “messenger RNA,” which is then translated into a protein that performs functions in the cell. The messenger RNA is a critical intermediate for making a gene into a protein. RNA editing technology allows us to disrupt that messenger RNA – and specifically the DUX4 messenger RNA – so that it cannot direct production of toxic DUX4 protein. In this proposal, we hypothesize that DUX4 RNA editing can be a powerful tool for making changes in the DUX4 RNA, and by doing so we can make it less toxic to muscle cells. We will determine if this system can effectively edit DUX4 RNA, and if those edits reduce muscle cell death as predicted. We expect this research will build a foundation for a potential FSHD therapeutic.

Related Material

Progress Update 1

Progress Update 2

SBIR CRISPR-Cas13 gene therapy and RNA editing for Facioscapulohumeral muscular dystrophy