Silencing the Disease Code | The Next Frontier of RNAi Therapeutics

RNA interference has moved from a Nobel Prize-winning discovery to a validated drug platform, and John Harris MD, PhD used that progress to ask Anastasia Khvorova PhD, Francesco De Rubertis PhD and Craig Shepherd what it will take to move siRNA beyond the liver and into a much wider range of diseases.

Khvorova described the chemistry and biology that made liver delivery possible, including chemical stabilization and receptor-mediated uptake, and pointed to the unusual durability now achievable with some siRNA medicines. That raises the possibility of replacing daily pills with treatments given only once or twice a year. The next frontier is extrahepatic delivery, with work advancing in tissues including skin, muscle, heart and the central nervous system.

The financing discussion showed how different investors approach the same scientific risk at different points in development. Shepherd reflected on Blackstone's large, structured investment in Alnylam after the platform had survived major setbacks and demonstrated clinical validation. De Rubertis explained Medicxi's asset-centric model, which generally favors focused programs with a clearer path to proof of concept rather than financing broad platforms for decades.

Across science and capital, the conversation came back to de-risking. RNAi is no longer being asked to prove that gene silencing can work in humans. The challenge now is delivering the right molecule to the right tissue, showing meaningful clinical benefit and matching the financing model to the time required to get there.