siRNA drugs are attacking "undruggable" proteins before they exist
Signals InboxAugust 25, 2026Biopharma
siRNA drugs attack disease before a problematic protein is made by silencing its messenger RNA. That changes the drug-design question from finding a molecule that fits a difficult protein surface to delivering a short RNA sequence into the right cells, opening targets that conventional chemistry often calls undruggable.
Most people have never heard of siRNA, but it’s going to change the face of medicine.https://t.co/5KsxO8MDlp
— Saloni (@salonium) August 25, 2026
Much drug development today involves developing chemicals to fit into proteins and block them. But this almost never turns out as planned: many drug candidates get…
Q1What was actually announced?
The mechanism is well established: the FDA explains RNA interference in its overview of siRNA medicines. Approved patisiran binds target mRNA and triggers its destruction, reducing production of the disease-causing protein rather than trying to block the finished protein.
Q2How big is the signal?
This is already a drug class, not a laboratory-only idea. Patisiran became the first approved siRNA therapeutic in 2018, followed by additional RNAi medicines including inclisiran. The platform can produce durable effects because one sequence can repeatedly silence matching messenger RNA inside cells.
Q3Why does it matter now?
Traditional small molecules need accessible pockets on proteins, while antibodies mostly target proteins outside cells or on cell surfaces. siRNA can in principle target the genetic message for almost any protein. That expands the target universe into transcription factors and other proteins with few obvious binding sites.
Q4What is the catch?
Delivery remains the bottleneck. The most successful siRNA drugs have largely focused on the liver because lipid nanoparticles and GalNAc conjugates can reach hepatocytes efficiently. Delivering enough RNA safely to tumors, the brain, muscle, or other tissues is much harder. Off-target effects, immune activation, and manufacturing also matter.
Q5What should we watch next?
Watch extrahepatic delivery platforms, late-stage programs against previously undruggable targets, dosing frequency, and combination approaches with gene editing or protein degradation. The category becomes much larger if reliable delivery expands beyond the liver without sacrificing safety.