Engineering editopes through programmable RNA editing toward tumor neoantigen generation.

Programmable RNA editing creates tumor-specific neoepitopes, enabling immune recognition and tumor control in melanoma models with 100% editing efficiency.

• Why it matters: Current neoepitope therapies face challenges in discovery and presentation, limiting clinical use; direct editing within cancer cells offers a promising alternative to generate immunogenic targets.
• What they did: Researchers developed SPEAR gRNAs to harness endogenous ADAR1 for precise A-to-I editing at specific transcript sites, generating neoepitopes called editopes, and applied this to melanoma antigen MART-1.
• The result: The approach restored T-cell recognition and controlled tumors in vivo, providing a new framework for neoepitope-based immunotherapy across multiple cancer types.