Volume 19 Issue 6, June 2020

Clinical trials of genome-editing agents — including CRISPR–Cas9 editors, zinc finger nucleases and TALENs — are pushing ex vivo, immuno-oncology and in vivo treatment frontiers.

Many G protein-coupled receptors (GPCRs) have endogenous peptide agonists, and modifying the sequence of these peptides has led to some successful therapeutics. In this Review, Davenport and colleagues discuss strategies to generate effective GPCR-targeted peptide therapeutics by introducing chemical novelty, extending plasma half-life, improving a therapeutic’s drug-like properties or generating biased ligands. These approaches could overcome some of the challenges in developing peptide therapeutics.

Communities of structural, metabolic and signalling proteins modulate downstream effects that result in differences in efficacy, adverse effects and resistance to therapy. This Review discusses how proteomic technologies are expanding our understanding of protein communities and of their responses to therapeutics.