CRISPR re-lengthens mRNA to expose prostate tumors
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- Researchers used a CRISPR Cas13 system to re-lengthen shortened SPSB1 mRNA in prostate cancer cells, reducing SPSB1 protein output and restoring the MHC-1 complex that marks tumors for T-cell attack.
- Duke University School of Medicine scientists led development of the first RNA-based CRISPR therapy that binds to mRNA without cutting it, preventing cancer cells from shortening the molecule's tail.
- In mice, the treatment let more T cells infiltrate prostate tumors and sharply improved response to immune checkpoint therapy, with the team reporting no detectable off-target effects.
- Eric J. Wagner, PhD, of University of Rochester Medicine, said the tool 'strengthens the immune system's ability to make the cancer go away' and could be paired with existing immunotherapies in prostate and other immune-cold tumors.
- The National Cancer Institute–funded study, published in Nature Biomedical Engineering, traces back to Wagner team's 12-year-old discovery that shortened mRNAs appear across many cancer types, first spotted in glioblastoma.
- Wilmot Cancer Institute and Roswell Park Comprehensive Cancer Center have committed pilot funding to test the re-lengthening approach in pancreatic cancer, another immunotherapy-resistant tumor type.
Why it matters: Prostate cancer is one of the most treatment-resistant 'immune-cold' tumors, where checkpoint inhibitors largely fail because tumor cells hide the MHC-1 signal T cells need. The mouse work demonstrates a way to restore that flag, potentially opening immunotherapy to a patient population with few options. Wilmot and Roswell have funded the next step in pancreatic cancer.
