In-Cell Penetration Selection-Mass Spectrometry Produces Noncanonical Peptides for Antisense Delivery.

ABSTRACT: Peptide-mediated delivery of macromolecules in cells has significant potential therapeutic benefits, but no therapy employing cell-penetrating peptides (CPPs) has reached the market after 30 years of investigation due to challenges in the discovery of new, more efficient sequences. Here, we demonstrate a method for in-cell penetration selection-mass spectrometry (in-cell PS-MS) to discover peptides from a synthetic library capable of delivering macromolecule cargo to the cytosol. This method was inspired by recent in vivo selection approaches for cell-surface screening, with an added spatial dimension resulting from subcellular fractionation. A representative peptide discovered in the cytosolic extract, Cyto1a, is nearly 100-fold more active toward antisense phosphorodiamidate morph

SUBMITTER: Schissel CK 

PROVIDER: S-EPMC10460143 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature