RNAi Therapeutics for Rare Neurodegenerative Disorders

Our divalent siRNA platform—engineered with optimal chemical modifications—has enabled broad, durable gene silencing in the central nervous system (CNS) following intrathecal delivery. These siRNAs achieve whole-brain distribution and sustain target silencing for up to six months in rodents and non-human primates. This work was recognized by Nature Biotechnology as one of the top 25 landmark papers of the past 25 years.

More than 14 clinical and preclinical programs now use this platform to treat diseases such as HD, ALS, AD, Parkinson’s disease, and others. We have also engineered multivalent siRNAs for targeted delivery to the lung and eye. In ocular models, a single injection is expected to provide more than 12 months of therapeutic benefit.

Our platform supports both monogenic and allele-specific silencing approaches. In collaboration with Dr. Robert Brown, we developed an siRNA targeting SOD1, which extended survival in the G93A ALS mouse model by up to a year (PMC11230209).

We have also developed siRNAs targeting PRNP, the gene encoding prion protein, in collaboration with Eric Minikel and Sonia Vallabh. This candidate, developed for an ultra-rare, orphan indication with little commercial interest, is expected to enter clinical trials this year with support from NIH-funded academic partnerships.

Another lead candidate targets MECP2, offering a potential treatment for MECP2 duplication syndrome. In preclinical models, siRNA-treated animals lived over a year, compared to only approximately three months for untreated controls.

We are proud to support initiatives like the N=1 Collaborative and partner with academic labs to ensure that transformative therapies can reach all patients—regardless of commercial potential.