Seattle-based Shape Therapeutics and the Rett Syndrome Research Trust (RSRT) announced a partnership to advance SHP-401, an investigational RNA editing gene therapy targeting the MECP2 R168X mutation, the single most common point mutation in Rett syndrome, accounting for approximately 10% of cases. Under the agreement, RSRT will fund translational studies in non-human primates (NHP) to evaluate biodistribution and on-target editing, with the goal of generating data to support IND-enabling studies. Financial terms were not disclosed.
SHP-401 uses Shape's RNAfix guide RNA platform, in which an AI-designed guide RNA recruits native adenosine deaminase acting on RNA (ADAR) enzymes to correct the R168X mutation at the RNA level, restoring full-length MeCP2 protein without permanent DNA alteration. The therapy is delivered intravenously via Shape's proprietary blood-brain barrier (BBB)-penetrant AAV5-derived capsid. In a preclinical mouse study posted to bioRxiv, Shape reported approximately 70% RNA editing of the R168X mutation throughout the brain following a single IV dose, with median lifespan extended from 50 days in untreated animals to as long as 174 days and a reported 88–93% reduction in risk of death. Transcriptome-wide profiling found no evidence of meaningful off-target editing, the company said. The NHP studies funded under this agreement will evaluate the AAV5-derived capsid's CNS biodistribution and on-target editing performance as the primary translational question before IND-enabling work begins.
The RSRT has pursued a portfolio approach to Rett syndrome genetic medicines, funding multiple competing platforms simultaneously. The trust previously provided a total of USD 9.1 million to Netherlands-based ProQR Therapeutics (Nasdaq: PRQR) to advance AX-2402, an RNA editing oligonucleotide targeting MECP2 mutations via its Axiomer platform — a chemically delivered, non-viral approach that contrasts with Shape's AAV-based delivery. RSRT also partnered with Apertura Gene Therapy in April 2025 to evaluate a transferrin receptor 1-targeted AAV capsid for Rett syndrome delivery, and with Emeryville, California-based Profluent Bio in November 2025 to design AI-engineered base editors targeting recurrent MECP2 mutations. The Shape collaboration adds an AAV-delivered ADAR RNA editing approach to that portfolio, distinct from both the gene replacement strategies in late-stage clinical development and the base editing programs at earlier stages.