Programmable mRNA 3'UTR engineering restores MHC-I and overcomes immune evasion in prostate cancer - PubMed
3 hours ago
- #prostate cancer
- #mRNA engineering
- #immune evasion
- Prostate cancer and other immune-cold tumors resist immune checkpoint therapies due to MHC-I downregulation, a key immune evasion mechanism.
- Researchers developed 3'UTRCES, a programmable RNA platform using CRISPR/dCas13, to manipulate mRNA alternative polyadenylation in vivo.
- They identified SPSB1 3'UTR shortening as a driver of MHC-I degradation via ubiquitination, without affecting PD-L1.
- LNP-delivered 3'UTRCES reversed SPSB1 shortening, restored MHC-I expression, and sensitized tumors to immune checkpoint therapy in mice.
- The therapy increased CD8+ T cell infiltration and antitumor activity, revealing APA-driven MHC-I suppression as a new immune escape mechanism.