Anastasia Khvorova

Key facts

• She founded the RTI Nucleic Acid Chemistry Center, described by the institution as the only non-profit center in North America able to synthesize complex RNAs at the scale needed for in vitro and in vivo studies.
• Divalent siRNA is two identical siRNAs linked together, invented in her lab and first reported in Nature Biotechnology in 2019; it distributes broadly in the brain after delivery into CSF.
• The Broad prion team approached her after a 2019 talk; her group screened siRNA sequences against mouse Prnp and human PRNP and filed patent WO2021173984 on several of them.
• Candidate 2439-s4: a single 348 microgram dose lowered whole-hemisphere human PrP to 17 percent residual in transgenic mice at 30 days and 52 micrograms gave 49 percent; 1 to 2 percent of the CSF dose stays in the brain.
• In prion-infected wild-type mice, a tool siRNA lowering PrP to 49 percent gave 2.7-fold longer survival with early chronic dosing and 64 percent longer survival with a single dose after symptom onset.
• FDA allowed the IND to proceed on 14 March 2025 for symptomatic patients, with a partial clinical hold on the pre-symptomatic protocol; the single-dose toxicology package limits the first trial to one dose.
• PRiSM is a phase 1 safety and dosing study funded through NINDS NeuroNEXT, with drug development funded by NIH grants and community donations to the Broad and Prion Alliance.
• Her lab states the divalent platform gives whole-brain silencing for up to six months in rodents and non-human primates, with more than 14 clinical and preclinical programs using it.
• She received the 2025 Else Kroner Fresenius Prize (2.5 million euros) for RNA therapeutics and said she would use it for new RNA molecules against toxic brain proteins, naming Huntington's disease.
• Her lab licensed an allele-specific siRNA for PLN-R14del cardiomyopathy to PLaN Therapeutics, a nonprofit owned by the PLN Foundation, in January 2026.
• Recent publications on the profile include a MECP2 duplication single-dose paper (Nature Communications, July 2026), a Huntington's disease paper (Science Translational Medicine, August 2026) and an albumin-binding dendrimer siRNA paper (NAR, September 2026).

Timeline

1. 2012Joins UMass Chan as professor.
2. 2019Divalent siRNA scaffold published in Nature Biotechnology; she presents it at the Broad in 2019 and the PRNP collaboration begins.
3. 2025IND for the siRNA candidate submitted by the Broad team.
4. 2025FDA allows a trial in symptomatic patients; partial hold on pre-symptomatic dosing.
5. 2025Else Kroner Fresenius Prize announced.
6. 2026PLN-R14del siRNA license to PLaN Therapeutics.
7. 2026Broad announces PRiSM is enrolling.
8. 2026Divalent siRNA for prion disease published in Nucleic Acids Research.
9. 2026NAR paper on albumin-binding dendrimer siRNA for the CNS.