GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE337nnn/GSE337438/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE337438GEOGSEfalseTumor-selective protein translation of mRNA drugs for targeted tumor therapymRNA-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.2026/07/07GSE337438GSM9855389GSM9855388GSM9855387GSM9855386GSM9855385GSM9855396GSM9855384GSM9855395GSM9855394GSM9855383GSM9855382GSM9855393GSM9855392GSM9855391GSM985539024676337438Homo sapiens