Employing RNA editing to engineer personalized tumor-specific neoantigens (editopes).

ABSTRACT: Increasing the quantity and immunogenicity of neoantigens in tumors is essential for advancing immunotherapy. However, engineering neoantigens remains challenging due to the need for precise, tumor-specific antigen modification without affecting normal cells. To tackle this challenge, we developed Short Precise-Encodable ADAR Recruiting (SPEAR) ADAR-engagers, an approach that uses short guide RNAs to engage the endogenous RNA editor ADAR1 and direct it to regions of mRNA targets known to encode MHC-presented peptides. By precisely editing adenosine-to-inosine (A-to-I) in these contexts, we effectively mutate specific epitopes into neoepitopes (which we now term "editopes"). As proof of concept, we targeted the known antigen MART-1 (Melanoma-Associated Antigen Recognized by T cells-1

SUBMITTER: Pecori R 

PROVIDER: S-EPMC12642233 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature