Anastasia Khvorova (born August 3, 1969) is a Russian-born American biochemist. She is a professor at the University of Massachusetts Chan Medical School, where she is a member of the RNA Therapeutics Institute and the Program in Molecular Medicine and holds the Remondi Family Chair in Biomedical Sciences. Khvorova's research focuses on the development of oligonucleotide- and RNA interference (RNAi)-based therapeutics.
Khvorova was born in Moscow, USSR on August 3, 1969. Khvorova earned her PhD in biochemistry from the Russian Academy of Sciences in 1994.
After relocating to the United States in 1995, she completed postdoctoral training at the University of Colorado Boulder.
Khvorova has held research and leadership positions in both academia and industry. In industry, she worked at Amgen and later, Dharmacon, a division of Thermo Fisher Scientific, where she advanced RNA biology and chemistry programs and served as Chief Scientific Officer. She later served as Chief Scientific Officer of RXi Pharmaceuticals.
In 2012, Khvorova joined UMass Chan Medical School as a professor in the RNA Therapeutics Institute and the Program in Molecular Medicine. She founded the Nucleic Acid Chemistry Center within the RNA Therapeutics Institute at UMass Chan Medical School, which provides RNA synthesis and chemistry expertise to academic research groups.
A central theme of Khvorova's work is the systematic study of chemical modifications to small interfering RNAs (siRNAs). Her laboratory has examined how alterations to ribose sugars, internucleotide linkages, and terminal groups affect RNA-induced silencing complex (RISC) loading and gene-silencing activity. This work contributed to the development of fully chemically modified siRNA scaffolds that retain RNAi potency while exhibiting improved metabolic stability and reduced off-target effects.
Her studies, in tandem with Phillip D. Zamore, helped define principles of thermodynamic asymmetry and strand selection during RISC assembly, clarifying how siRNA duplex design influences guide strand incorporation and silencing efficiency.
Khvorova has made key contributions to strategies for delivering RNAi therapeutics beyond the liver. Her laboratory demonstrated that extensive chemical stabilization is required for effective conjugate-mediated delivery and identified lipid and other hydrophobic conjugates that enable functional RNAi activity in extrahepatic tissues.
This work established that conjugate hydrophobicity and chemical composition govern systemic distribution through endogenous lipid transport pathways, enabling silencing activity in tissues such as the heart, muscle, central nervous system, eye, kidney, lung, and placenta.
Khvorova's research has also explored novel backbone chemistries designed to enhance tissue retention and specificity. Her group characterized extended nucleic acid (exNA) and internally constrained vinyl phosphonate linkages, demonstrating that these chemistries improve extrahepatic accumulation and support allele-selective gene silencing in vivo. These approaches have been applied to therapeutic strategies for dominantly inherited neurological and genetic disorders.
More recently, Khvorova introduced multivalent and divalent siRNA architectures in which increased molecular valency, combined with optimized chemical modification, produces prolonged tissue retention and sustained gene silencing following a single administration. These designs have been applied to multiple extrahepatic targets and represent an approach to extending the durability of RNAi therapeutics.
In parallel with applied therapeutic research, Khvorova has contributed to the understanding of off-target effects in RNAi. Her work demonstrated that seed-mediated interactions are a primary driver of miRNA-like off-target silencing, informing both computational prediction methods and chemical strategies to improve siRNA specificity.
Collectively, these lines of research have contributed to defining design principles that underlie contemporary RNAi-based therapeutics.
Therapeutic RNA delivery beyond the liver remains a major challenge in the field. To address these challenges, Khvorova's research centers on chemical modification of therapeutic RNAs to improve stability, specificity, and delivery, enabling delivery to tissues that have traditionally been difficult to target, including the brain, heart, muscle, lung, placenta, and eye. Khvorova is known for research that helped define principles of siRNA design, strand selection, and chemical modification. Her work has contributed to the development of RNA-based approaches for the treatment of genetic, neurodegenerative, and infectious diseases, including Huntington's disease.
She has authored more than 130 peer-reviewed publications across academic and industry settings and has more than 49,000 citations on Google Scholar. Her research includes highly cited articles in journals such as Cell, Nature, Nature Biotechnology, Nature Communications, and Proceedings of the National Academy of Sciences.
Khvorova has co-founded several biotechnology companies, including Atalanta Therapeutics, which develops RNA-based approaches for neurodegenerative diseases using branched siRNA technology licensed from UMass Chan Medical School, as well as Comanche Biopharma, which develops RNA-based therapeutics for preeclampsia based on work done by Drs. Anastasia Khvorova and Melissa J. Moore. Khvorova also serves on the scientific advisory boards of Advirna, Aldena, Alltrna, Prime Medicine, and Evox Therapeutics. Khvorova is listed as an inventor on more than 180 issued patents and several hundred patent applications related to RNA chemistry and therapeutic delivery. She is a Fellow of the National Academy of Inventors.