Industry-leading RNA editing activity in the CNS of both mice and non-human primates highlights the broad applicability and therapeutic potential of the RNAfix® platform in CNS diseases
Preclinical data showcases first demonstration of systemically delivered RNA editing in a primate brain, enabled by a blood-brain barrier (BBB) crossing AAV5 variant
TruStable™ system demonstrates greatly increased scalability and consistency vs existing methods of AAV production across multiple serotypes
SEATTLE, May 16, 2025 (GLOBE NEWSWIRE) -- Shape Therapeutics, a leader in RNA-based gene therapy, today announced that the Company presented data demonstrating the potential of its RNAfix® platform to restore protein function and reduce pathogenic proteins implicated in multiple neurological diseases, and to deliver the therapies efficiently with novel brain-targeting AAV capsids. The Company also presented data highlighting the versatility of its TruStable™ platform to achieve high quality vectors with improved process yield and consistency, resulting in overall reduced costs. These data were shared in multiple oral and poster presentations at the American Society of Gene and Cell Therapy (ASGCT) 28th Annual Meeting taking place in New Orleans, Louisiana, May 13-17, 2025.
“The preclinical data we presented at this year’s ASGCT meeting further highlight our transformational genetic medicine and scalable manufacturing platforms,” said David Huss, Ph.D., CSO and acting CEO of Shape Therapeutics. “We were particularly pleased to showcase our novel brain-penetrating capsids that represent the first demonstration of systemically delivered RNA editing in a primate brain, the highest primate neuronal targeting by a blood-brain barrier-crossing AAV variant and the highest targeting of the primate substantia nigra seen with any novel brain therapy. These data, coupled with the AAV vectors produced via our TruStable™ producer platform, underscore the high-value, low-cost potential of our gene therapy assets.”
Key findings from the presentations at ASGCT include:
AAV5-Based Capsid Variants:
- Novel AAV5-based capsids generated by Shape’s AAV.ai platform efficiently cross the BBB of cynomolgus macaques after IV injection while showing extensive liver and DRG detargeting.
- Two capsids, SHP-DB1 and SHP-DB2, showed particularly strong delivery to deep brain regions, with payload expression observed in >96% of all neurons in the substantia nigra, the critical brain region in Parkinson’s disease.
- SHP-DB1 and SHP-DB2 delivered efficient targeted RNA editing across the NHP brain from a single IV injection, with up to 88% editing observed in RNA from brain biopsies.
Programmable RNA Editing in the CNS:
- Shape’s RNAfix® platform uses guide RNAs (gRNAs) that harness the natural Adenosine deaminases acting on RNA (ADAR) enzyme to therapeutically edit sites in patient RNA.
- gRNAs engineered with AI for potency and specificity enable therapeutic levels of protein modulation in multiple CNS diseases, demonstrating the broad applicability and enormous therapeutic potential of the RNAfix® platform for CNS diseases.
- In a mouse model of Rett syndrome, gRNAs targeting the R168X mutation in the MECP2 gene achieved broad distribution throughout the brain following IV injection, enabling 52-69% editing of the target mRNA and restoring full-length MECP2 protein in ~39% of all cells.
- In a mouse model of neurodegenerative disease, RNAfix gRNAs achieved >70% reduction of targeted pathogenic protein in iPSC-derived glutamatergic neurons and >50% protein knockdown in the mouse brain following a single systemic AAV dose. In a third neurological disease, RNAfix gRNAs achieved >90% protein knockdown in human neurons and >60% knockdown in mouse brain.
- RNAfix is designed for a “one-and-done” therapeutic approach, supported by full maintenance of high efficiency editing in the mouse brain one year post-dosing.
TruStable™ AAV Manufacturing:
- Shape’s fully stable AAV producer cell line platform, TruStable, was shown to generate higher quantities and quality of material than a traditional transient transfection method.
- TruStable™ production cell line produced ~15-fold more AAV with ~3-fold higher packaging percentage than the comparator triple transfection system, resulting in ~30-fold more material generated per cell culture volume after final purification.
- In-vitro potency results suggest that the TruStable™ derived material is ~2-fold as potent as triple transfection when comparing the upper asymptote of the 4PL dose response curve.
- The TruStable™ producer cell line can now efficiently produce multiple AAV serotypes by integrating Adenoviral L4 helper factor, which broadens the applicability of the platform and support high-titer, reproducible production of diverse AAV vectors.
About Shape Therapeutics
ShapeTX is an AI-driven genomic medicines company focused on creating curative and transformative medicines through its programmable RNA editing technology. By focusing on three differentiated pillars of value, ShapeTX utilizes its RNAfix® technology, targeted AAV.ai delivery system and TruStable™ manufacturing platform to advance a strong internal pipeline of RNA therapeutics across a wide range of diseases, including ABCA4-related diseases and neurological disorders. You can find us at shapetx.com and on LinkedIn and X.
Investor Contact:
Anne Marie Fields
Precision AQ
212-362-1200
Annemarie.fields@precisionaq.com
Media Contact:
info@shapetx.com
