New frontiers in extracellular protein degradation

Several academic groups have recently published new techniques for degrading extracellular proteins that could ease some of the pain points of current methods. The advances include simplified manufacturing, increased potency and improved cell specificity.

The first generation of targeting chimeras (TACs), known as PROTACs, degrade intracellular protein targets. Since their discovery over 20 years ago, academics and companies have developed several PROTAC-adjacent methods, including some that degrade extracellular protein targets. The benefit of degrading a cell surface or secreted target is that destroying the protein eliminates all of its functions; whereas as inhibiting a specific site on the protein may allow some functions to persist. Also, the duration of effect for a degrader is typically longer than an inhibitor, as the target protein would need to be synthesized again before its levels and function could be restored...