Engineering editopes through programmable RNA editing toward tumor neoantigen generation

ABSTRACT: Neoepitope-based therapies hold great promise for cancer immunotherapy because they target tumor-specific mutations and elicit potent anti-tumor T-cell responses. However, their clinical implementation remains limited by the complexity of neoepitope discovery and uncertainty regarding presentation by tumor cells. A potential alternative is the generation of immunogenic neoepitopes directly within cancer cells through programmable engineering. Here, we develop Short Precise-Encodable ADAR Recruiting (SPEAR) gRNAs that harness endogenous ADAR1 to direct precise adenosine-to-inosine (A-to-I) editing at selected transcript sites. Using these gRNAs, we demonstrate the generation of immunogenic neoepitopes through RNA editing at the transcript level, termed editopes. In a proof-of-concept model

SUBMITTER: Riccardo Pecori 

PROVIDER: S-SCDT-10_1038-S44318-026-00870-5 | biostudies-other |

REPOSITORIES: biostudies-other