Expression of a RAS degrader via synthetic nanocarrier-mediated mRNA delivery reduces pancreatic tumors.

ABSTRACT: Therapeutic gene expression can address many of the challenges associated with the controlled delivery of intracellularly active biologics, such as enzymes that degrade RAS for treatment of RAS-driven cancers. Here, we demonstrate that an optimized synthetic nonviral gene delivery platform composed of poly(ethylene glycol)-b-poly(propylene sulfide) (PEG-PPS) can block copolymers conjugated to a dendritic cationic peptide (PPDP2) for nontoxic delivery and therapeutic expression of mRNA within human pancreatic cancer cells and tumors. The naturally occurring bacterial enzyme RAS/RAP1-specific endopeptidase (RRSP) is a potent RAS degrader that specifically targets all RAS isoforms. Using PPDP2, rrsp-mRNA is delivered to human pancreatic cells resulting in RRSP protein expression

SUBMITTER: Escher TE 

PROVIDER: S-EPMC11212117 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature