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Omics · study · 2026

Tumor-selective protein translation of mRNA drugs for targeted tumor therapy

Listed in NCBI GEO

mRNA-based therapies necessitate precise, specific, and patient-friendly control of therapeutic protein translation to ensure treatment safety and efficacy.

Description

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.

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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.

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Life Sciences
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Cancer 65%
Provenance · 1 source records, 8 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE33743811 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[disease].local:disease:cancerenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (65%)
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencingsource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[organism].NCBITaxon:9606source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
descriptionsource · NCBI GEOconnector:ncbi_geo@1.0.0/summary
publication_datesource · NCBI GEOconnector:ncbi_geo@1.0.0
titlesource · NCBI GEOconnector:ncbi_geo@1.0.0/title