This story is one of a series on how we cleanse–from organizing your house to washing your tuchus.
Of all the existential intergalactic threats ever faced by the crew of the starship Enterprise, perhaps none smolders more brightly in the minds of classic Star Trek followers than the gaping, antiproton-beam-backlit maw of the Planet Killer. What could be more memorable, after all, than a miles-long, barrel-shaped machine that prowls through room, inhaling planets through one extremity and chopping them into rubble to be expelled out the other? Now imagine a microscopic version of that and you’ve got yourself a proteasome, one of the most essential molecular machines inside the human body. Instead of broken off planets though, it hacks apart proteins.
This tubular apparatus of orderly extermination is basically a cellular garbage disposal, continuing thousands of damaged, misfolded, or otherwise obsolete proteins from piling up inside your cells like so much interplanetary space junk. Over the past two decades, as biochemists began figuring out how this natural trash-clearing system operates, some discovered ways to trick it into aborting nearly any protein they wanted.
Today, investors are running billions of dollars into what many hope will be the next generation of blockbuster medications based on programmable proteasomes. In the last few years, nearly every major pharmaceutical firm has begun negotiating deals with startups was engaged in targeted protein degradation–as the rapidly expanding drug strategy is known–or spinning up their own internal growing programs. Whereas tiny molecules like ibuprofen and benadryl gum up proteins, and Crispr knocks out the genes that attain proteins, protein degraders offer a radical new space to selectively reach into cells and onslaught a whole host of historically difficult-to-treat diseases brought about by misbehaving molecules, from Alzheimer’s to Parkinson’s to many types of cancer.