After the stunning commercial success of semaglutide-based obesity drugs, the race is on in the biotech world to find a more durable solution that does not require frequent injections. The idea is to silence selected genes without irreversibly intervening on DNA. Basically, it would not involve genetically fixing the target sequence, but preventing its expression through a phenomenon called RNA interference. As is well known, a classical-type gene, in order to express itself, must be transcribed into RNA and then translated into protein. Blocking the transcript, therefore, cancels its action, as Nobel laureates Craig Mello and Andrew Fire have realized.

Among the companies working on RNA interference with this goal, some have targeted a gene that is normally expressed in the brain (GPR75). People who possess a naturally mutated version tend to have a low body mass index, so by interfering with the gene’s transcripts, researchers hope to mimic this effect. Other companies are targeting a gene expressed in the liver (INHBE) that is associated with waist to hip ratio.

If successful, the anti-obesity revolution would enter a new phase, as STAT writes, “away from weekly drugs targeting hormones to medications that could be given much less frequently — twice a year or even less — and pinpoint genetic contributors to weight”.