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Can we switch off diseases? siRNA drugs are, in my view and @jacobtref.bsky.social’s too, one of the most exciting developments in medicine. So we decided to do an episode!

siRNA drugs can ‘silence’ harmful genes in the body. And there are lots of cases where you might want to silence genes: - Infectious diseases, where you can silence pathogen proteins or human proteins that pathogens depend on - Rare genetic diseases, to silence the production of mutated proteins

What’s even better is that siRNA drugs are: • Potentially tunable, meaning you could reduce the production of a protein, rather than silencing it entirely • Programmable, meaning you can quickly switch out which gene it targets by changing its sequence

• Long-lasting: some drugs last for months, even half a year, with a single injection • Off-the-shelf: they typically don’t involve complicated surgeries or procedures, because of the way they’re delivered in the body

Today, siRNA drugs are largely used to treat liver diseases, partly because that’s the easiest starting point. And they are extremely effective at it. One example is for cholesterol: siRNA drugs reduce PCSK9 levels by around 70%, reducing cholesterol levels by 50-60%, beyond the effect of statins.