ACS Chemical Biology, Journal Year: 2024, Volume and Issue: unknown
Published: Dec. 20, 2024
Oligonucleotides are a rapidly emerging class of therapeutics. Their most well-known examples informational drugs that modify gene expression by binding mRNA. Despite inducing proximity between biological machinery and mRNA when applied to modulating expression, oligonucleotides not typically labeled as "proximity-inducing" in literature. Yet, they have recently been explored building blocks for multispecific proximity-inducing (MPIDs). MPIDs unique because can direct endogenous destroy targeted molecules cells, contrast traditional inhibit only their functions. The mechanism action has enabled the targeting previously "undruggable" molecular entities cannot be effectively inhibited. However, development must ensure these will selectively potent, destruction-based toward intended targets over healthy tissues avoid causing life-threatening toxicities. emerged promising design sequence-controlled rationally designed program interactions. In this Review, we examine emergence oligonucleotide-containing induction space, which dominated antibody small molecule MPID modalities. Moreover, developed candidates immunotherapy protein degradation discussed demonstrate utility expanding scope selectivity toolbox. Finally, discuss programming "AND" gates into oligonucleotide scaffolds encode conditional responses potential incorporated MPIDs, further enhance selectivity, thus increasing drug category.
Language: Английский