Into the Dark: Finding Novel Drug Targets Within the Depths of Our Proteome

Drug discovery has never had a richer therapeutic toolbox. Antibody-drug conjugates, antisense oligonucleotides, CRISPR therapeutics, RNA medicines, CAR-T cells, PROTACs, and molecular glues have transformed how medicine can manipulate biology. Yet every modality still depends on the same prerequisite: a biologically meaningful target. Many of the roughly 20,000 canonical human genes and their protein products are poor therapeutic candidates because they lack disease relevance, cannot be addressed by certain modalities, or cause unacceptable side effects when manipulated.

Perhaps the limiting factor is not only how we drug biology, but how much biology we know.