NF1 RNA Repair Based on Therapeutic Ribozymes

Ribozymes, ribonucleic acid (RNA) molecules with catalytic properties can be modified to specifically bind to a target RNA of choice, split this RNA at a specific site into two parts, and replace one part with another RNA sequence that is attached to the ribozyme. This trans-splicing ability of engineered ribozymes establishes a potential strategy for therapeutic RNA repair. This project builds upon the concept of using bioengineered trans-acting ribozymes to target faulty transcripts of the NF1 gene that carry mutations causing neurofibromatosis type 1 (NF1). We aim to restore function to the NF1 gene product for a variety of patient derived NF1 mutations in human cell lines. As part of the ribozyme design, we will consider and analyze potential obstacles on the path to NF1 clinical application, including delivery of the therapeutic ribozymes, avoidance of off-target effects, and minimization of a possible immune response. We envision our research to constitute the first step towards a novel RNA-based therapy for the treatment of NF1.

 

Investigators

André Leier, PhD

University of Alabama, Birmingham

Ulrich Muller, PhD

University of California, San Diego

André Leier, PhD

University of Alabama, Birmingham

Ulrich Muller, PhD

University of California, San Diego

Current Stage

Discovery

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