Endosomal disentanglement of a transducible artificial transcription factor targeting endothelin receptor A.

ABSTRACT: Cell-penetrating peptides (CPPs) hold great promise for intracellular delivery of therapeutic proteins. However, endosomal entrapment of transduced cargo is a major bottleneck hampering their successful application. While developing a transducible zinc finger protein-based artificial transcription factor targeting the expression of endothelin receptor A, we identified interaction between the CPP and the endosomal membrane or endosomal entanglement as a main culprit for endosomal entrapment. To achieve endosomal disentanglement, we utilized endosome-resident proteases to sever the artificial transcription factor from its CPP upon arrival inside the endosome. Using this approach, we greatly enhanced the correct subcellular localization of the disentangled artificial transcription factor, sig

SUBMITTER: Bippes CC 

PROVIDER: S-EPMC8821953 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature