Shape Therapeutics and Rett Syndrome Research Trust Announce Partnership to Advance a One-Time AI-Designed RNA Editing Therapy for Rett Syndrome
Collaboration will evaluate Shape's intravenously delivered RNAfix® gene therapy designed to correct the MECP2 R168X mutation in non-human primates (NHP)
SEATTLE, Aug. 06, 2026 (GLOBE NEWSWIRE) -- Shape Therapeutics, a leader in RNA editing-based gene therapy, today announced a partnership with the Rett Syndrome Research Trust (RSRT) to advance SHP-401, an investigational one-time gene therapy for Rett syndrome. Under the agreement, RSRT will fund translational studies to evaluate Shape’s RNAfix® guide RNA, designed to leverage native human ADAR enzymes to correct the MECP2 R168X mutation, paired with Shape’s proprietary blood-brain-barrier (BBB)-penetrant AAV5-derived capsid for delivery to the central nervous system. The studies are designed to generate supportive data to advance SHP-401 toward IND-enabling studies.
Rett syndrome is a rare, severe neurodevelopmental disorder that emerges in early childhood, predominantly in girls, characterized by developmental regression, loss of speech and hand use, motor dysfunction, and reduced life expectancy. It is caused primarily by mutations in the MECP2 gene and loss of functional MeCP2 protein. The R168X mutation is the single most common causal point mutation found in Rett patients, accounting for approximately 10% of cases. Using a proprietary generative AI model, Shape designed a guide RNA payload that recruits the adenosine deaminase acting on RNA (ADAR) enzyme to correct the R168X mutation at the RNA level and restore full-length MeCP2 protein.
In a recent preclinical study posted to bioRxiv titled “Rett syndrome lifespan extension in mice via AI-guided ADAR editing”, Shape reported that RNAfix® AI-designed gRNAs targeting MECP2 achieved approximately 70% RNA editing of the R168X mutation throughout the brain following a single intravenous dose in a mouse model of Rett syndrome, restoring full-length MeCP2 protein and substantially improving Rett-like phenotypes, including mobility and tremor. Treatment markedly extended survival, increasing median lifespan from 50 days in untreated animals to as long as 174 days and reducing the risk of death by 88–93%. Transcriptome-wide profiling found no evidence of meaningful off-target editing, supporting the specificity of the approach as it advances toward the clinic.
RSRT is dedicated to advancing genetic medicines that address the underlying root cause of the disorder and is particularly interested in delivery technologies that can achieve diffuse biodistribution. Through this collaboration, Shape and RSRT will evaluate Shape’s novel AAV5-derived capsid for intravenous delivery of the MECP2 R168X RNAfix gRNA in non-human primates, with the goals of characterizing biodistribution and on-target editing. Successful completion of the program is expected to generate data that will support further advancement of the program toward the clinic.
“The Shape team is excited to work with RSRT on advancing a precise RNA editing therapy for Rett syndrome,” said Adrian Briggs, Chief Technology Officer at Shape Therapeutics. “Our unique AAV-delivered ADAR-based editing platform has shown incredible efficacy in mouse models of this devastating disease, and we are greatly looking forward to moving the program closer to clinic translation in partnership with RSRT.”
“RSRT was an early believer in the power of ADAR-mediated RNA editing having funded academic investigators Gail Mandel and Peter Beal beginning well over a decade ago. We are excited to now partner with Shape and hope to see this program advance to the clinic,” shared Monica Coenraads, RSRT’s CEO.
About Shape Therapeutics
Shape Therapeutics is leveraging AI to develop new payload, delivery, and manufacturing technologies for the gene therapy industry. Alongside the company's own RNA-targeting gene therapy portfolio, Shape's platform includes AAV capsids with enhanced tropism and penetration profiles, enabling delivery of genetic medicines to previously inaccessible tissues. The company is headquartered in Seattle, Washington. You can find us at shapetx.com and on LinkedIn.
About Rett Syndrome Research Trust
The Rett Syndrome Research Trust is the only non-profit organization exclusively focused on advancing genetic medicines for Rett syndrome. It is the largest funder of Rett research worldwide. In 2024 RSRT launched an initiative to bring three genetic medicines, beyond the current gene therapies, to clinical trials by 2028. RSRT’s mission is clear, urgent, and personal: to cure Rett syndrome and transform the lives of the people we love.
Related ShapeTX publications:
- Savva, Y.A., Booth, B.J., Shumaker, L. et al. Rett syndrome lifespan extension in mice via AI-guided ADAR editing. bioRxiv (2026). https://doi.org/10.64898/2026.06.23.734060
- Jiang, Y., Bagepalli, L.R., Banjanin, B.S. et al. Generative machine learning of ADAR substrates for precise and efficient RNA editing. bioRxiv (2024). https://doi.org/10.1101/2024.09.27.613923
- Cao, Y., Bagepalli, L.R., Savva, Y.A. et al. Helix: a structure-aware deep learning model for accurate prediction of A-to-I RNA editing by endogenous ADARs. bioRxiv (2025). https://doi.org/10.64898/2025.12.18.695251
- Byrne, S.M., Burleigh, S.M., Fragoza, R. et al. An engineered U7 small nuclear RNA scaffold greatly increases ADAR-mediated programmable RNA base editing. Nat Commun 16, 4860 (2025). https://doi.org/10.1038/s41467-025-60155-z
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