ArticleNature biomedical engineering2025
Extension of replicative lifespan by synthetic engineered telomerase RNA in patient induced pluripotent stem cells.
Article in Nature biomedical engineering, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Primer- and template-independent RNA polymerization by terminal nucleotidyltransferase TENT4B.Nucleic acids research · 2026Article
- Saturating variant analysis of TERC redefines the human telomerase reverse transcription mechanism.bioRxiv : the preprint server for biology · 2026Article
- Telomerase modRNA Offers a Novel RNA-Based Approach to Treat Human Pulmonary Fibrosis.Aging cell · 2025Article
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Authors and funding
2 authors.
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Abstract
RNA engineering has yielded a new class of medicines but faces limitations depending on RNA size and function. Here we demonstrate the synthesis and enzymatic stabilization of telomerase RNA component (TERC), a therapeutically relevant long non-coding RNA (lncRNA) that extends telomere length and replicative lifespan in human stem cells. Compared with therapeutic mRNAs, engineered TERC RNA (eTERC) depends on avoiding nucleoside base modifications and incorporates a distinct trimethylguanosine 5' cap during in vitro transcription. We show that the non-canonical polymerase TENT4B can be repurposed to enzymatically stabilize synthetic RNAs of any size by catalysing self-limited 2'-O-methyladenosine tailing, which is critical for optimal eTERC function in cells. A single transient exposure to eTERC forestalls telomere-induced senescence in telomerase-deficient human cell lines and lengthens telomeres in induced pluripotent stem cells from nine patients carrying different mutations in telomere-maintenance genes, as well as primary CD34
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Registered trials
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