Targeted cancer ablation via programmable sensing of amplified oncogenic RNA

ORCA enables RADAR-based sensing of amplified oncogenic RNA to ablate high-MYC colorectal cancer cells, with in vivo AAV delivery suppressing tumor growth and prolonging survival.

• Why it matters: Targeting cancer cells by their oncogenic drivers is difficult, especially for transcripts from oncogenes like MYC that are hard to drug directly.
• What they did: ORCA couples RADAR sensors for amplified MYC, FGFR2, and wild-type KRAS transcripts with conditional therapeutic payload expression, then tests MYC-driven CRC ablation using anti-CD19 CAR-T and enzyme-prodrug approaches.
• The result: In subcutaneous xenografts and CRC liver metastasis models, AAV-delivered ORCA suppresses tumor growth and prolongs survival, supporting programmable RNA sensing as an actionable targeting strategy.

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