Researchers at Boston Children's Hospital and Harvard developed a synthetic, stabilized version of telomerase RNA (TERC) — a long non-coding RNA critical for telomere maintenance. Using optimized in vitro transcription with a trimethylguanosine cap and enzymatic stabilization via the non-canonical polymerase TENT4B, the engineered TERC (eTERC) was functionally active without nucleoside base modifications. A single transient dose of eTERC lengthened telomeres and delayed senescence in telomerase-deficient human cell lines, induced pluripotent stem cells from nine patients with mutations in telomerase-associated genes, and primary CD34+ blood stem/progenitor cells. The work establishes a platform for producing functional synthetic long non-coding RNAs and points toward potential RNA-based therapies for diseases driven by short telomeres.
