Project description:mRNA-based therapies necessitate precise, specific, and patient-friendly control of therapeutic protein translation to ensure treatment safety and efficacy. However, achieving tumor-specific mRNA translation regulation remains a significant challenge. Herein, we developed an mRNA 2’-OH cloaking reagent, CR-3, enabling tumor-specific regulation of mRNA translation. CR-3 can efficiently and effectively block the translational capacity of mRNA. Within tumor cells exhibiting high expression of NAD(P)H quinone dehydrogenase 1 (NQO1), the translational ability of this mRNA can be almost fully restored. The translational efficiency of cloaked mRNA in tumor cells is more than 100-fold greater than that in normal cells. Additionally, 2’-OH cloaking enhances the stability and half-life of mRNA, resulting in a 49% increase in target protein production. The cloaked apoptogenic protein BAX mRNA achieved tumor cell-specific clearance, and mitigated systemic toxicity in both subcutaneous xenograft mouse model and chemically induced mouse model of hepatocellular carcinoma, in contrast to conventional non-cloaked BAX mRNA. This approach may pave the way for the development of safe, convenient, and responsive tumor-targeted mRNA therapeutics.

2026-07-07 | GSE337438 | GEO

ilGypAcer

Project description:Gypsonoma aceriana (white cloaked tortrix), ilGypAcer

| PRJEB112678 | ENA