Combination of KRAS ASO and RIG-I agonist in extracellular vesicles transforms the tumor microenvironment towards effective treatment of KRAS-dependent cancers.

ABSTRACT: Rationale: Mutations in the KRAS gene drive many cancers, yet targeting KRAS mutants remains a challenge. Here, we address this hurdle by utilizing a nucleic acid-based therapeutic strategy delivered via extracellular vesicles (EVs) to simultaneously inhibit KRAS mutants and activate the RIG-I pathway, aiming to enhance anti-tumor immunity. Methods: Antisense oligonucleotides against KRAS mutants (KRAS ASOs) and RIG-I agonist immunomodulatory RNA (immRNA) were loaded into EVs and administered to KRAS-mutant cancer models. The therapeutic effects were assessed in colorectal and non-small cell lung cancer (NSCLC) tumor models, as well as patient-derived pancreatic cancer organoids. Immune responses were evaluated by analyzing tumor micr

SUBMITTER: Phung CD 

PROVIDER: S-EPMC12203666 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature