CRISPR-Based RNA Editing Restores Immune Visibility in 'Cold' Prostate Tumors

Researchers led by teams at Duke University School of Medicine and the University of Rochester published in Nature Biomedical Engineering a CRISPR-Cas13-based RNA-targeting tool that restores MHC-I expression on prostate cancer cells, making immunologically 'cold' tumors visible to the immune system. In prostate cancer, the protein SPSB1 (overproduced due to 3′UTR shortening of its mRNA) degrades the MHC-I complex that flags tumor cells to T cells. Rather than cutting DNA or RNA, the tool binds the SPSB1 mRNA's 3′UTR to block the shortening machinery, restoring the transcript's normal length, reducing SPSB1 protein, and re-exposing MHC-I. In mouse models, this significantly increased T-cell infiltration and improved response to immune checkpoint therapy, with no off-target effects detected in the review.