Can we switch off diseases?

What if treating diseases was as simple as telling your cells to stop making a harmful protein? That’s the premise of siRNA, a technology that silences genes without changing DNA. Just a single dose of siRNA can last for months. Better, it can be reprogrammed to silence a different gene or mutation by simply switching its sequence.

In this episode, Jacob and Saloni explore why it took so long for siRNA to be turned into drugs, why most siRNA drugs so far have targeted liver diseases, and whether they could eventually be used to treat many diseases, from infections to heart disease to rare diseases to cancers.

Hard Drugs is a podcast from Works in Progress about medical innovation presented by Saloni Dattani and Jacob Trefethen.

You can watch or listen on YouTube, Spotify, or Apple Podcasts.

Chapters:

• (00:00) - Introduction
• (09:58) - siRNA trivia
• (28:14) - The 20 year journey to make siRNA drugs
• (36:07) - Which diseases could siRNA treat?
• (50:45) - Programmable, long-lasting, scaleable drugs
• (54:32) - Can siRNA solve everything?
• (01:08:23) - Conclusion

Saloni’s substack newsletter: https://www.scientificdiscovery.dev/

Jacob’s blog: https://blog.jacobtrefethen.com/

Acknowledgements:

• Graham Bessellieu, video editor
• Abhishaike Mahajan, cover art
• Atalanta Arden-Miller, art direction
• David Hackett, composer

Articles

• Jacob Witten (2026). The kill switch for harmful genes. Works in Progress. https://worksinprogress.co/issue/the-kill-switch-for-harmful-genes/
• Virginie Baylot et al. (2024) Between hope and reality: treatment of genetic diseases through nucleic acid-based drugs. https://www.nature.com/articles/s42003-024-06121-9
• Chokwassanasakulkit et al. (2024) SiRNAs as antiviral drugs – Current status, therapeutic potential and challenges. https://doi.org/10.1016/j.antiviral.2024.106024
• Antonio Fontanellas et al. (2025) RNA-based therapies in liver metabolic diseases. https://doi.org/10.1136/gutjnl-2023-331742