Phenylboronic Acid-Functionalized Polyplexes Tailored to Oral CRISPR Delivery.

ABSTRACT: Effective delivery of the CRISPR-Cas9 components is crucial to realizing the therapeutic potential. Although many delivery approaches have been developed for this application, oral delivery has not been explored due to the degradative nature of the gastrointestinal tract. For this issue, we developed a series of novel phenylboronic acid (PBA)-functionalized chitosan-polyethylenimine (CS-PEI) polymers for oral CRISPR delivery. PBA functionalization equipped the polyplex with higher stability, smooth transport across the mucus, and efficient endosomal escape and cytosolic unpackaging in the cells. From a library of 12 PBA-functionalized CS-PEI polyplexes, we identified a formulation that showed the most effective penetration in the intestinal mucosa after oral gavage to mice. The optimized f

SUBMITTER: Yoshinaga N 

PROVIDER: S-EPMC10375565 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature