Evidence map›Paper›PMID 25614443›Full record

ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2015

Transient delivery of modified mRNA encoding TERT rapidly extends telomeres in human cells.

John Ramunas, Eduard Yakubov, Jennifer J Brady, Stéphane Y Corbel, Colin Holbrook, Moritz Brandt, Jonathan Stein, Juan G Santiago, John P Cooke, Helen M Blau

Abstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed, 1 pooled it
8.1field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

71 citing papers in PubMed, 1 synthesis or guideline pooled it, 116 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Review
  5. Article
  6. Article
  7. Telomerase mRNA-Lipid nanoparticles attenuate neuroinflammation after traumatic brain injury in mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Article
  8. Telomerase mRNA therapy protects human skin against radiation-induced DNA damage.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Causality of Aging Hallmarks.Aging and disease · 2025
    Review
  16. Article
  17. Review
  18. Review
  19. Review
  20. Article

11 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 2 countries.

John Ramunas*Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Clinical Sciences Research Center, Stanford University School of Medicine, Stanford, California, USA; Falk Cardiovascular Research Center, Stanford University School of Medicine, Stanford, California, USA; SpectraCell Laboratories, Inc., Houston, Texas, USA; and Department of Mechanical Engineering, Stanford University, Stanford, California, USA.
Eduard Yakubov*Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Clinical Sciences Research Center, Stanford University School of Medicine, Stanford, California, USA; Falk Cardiovascular Research Center, Stanford University School of Medicine, Stanford, California, USA; SpectraCell Laboratories, Inc., Houston, Texas, USA; and Department of Mechanical Engineering, Stanford University, Stanford, California, USA.
Jennifer J Brady*Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Clinical Sciences Research Center, Stanford University School of Medicine, Stanford, California, USA; Falk Cardiovascular Research Center, Stanford University School of Medicine, Stanford, California, USA; SpectraCell Laboratories, Inc., Houston, Texas, USA; and Department of Mechanical Engineering, Stanford University, Stanford, California, USA.
Stéphane Y Corbel*Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Clinical Sciences Research Center, Stanford University School of Medicine, Stanford, California, USA; Falk Cardiovascular Research Center, Stanford University School of Medicine, Stanford, California, USA; SpectraCell Laboratories, Inc., Houston, Texas, USA; and Department of Mechanical Engineering, Stanford University, Stanford, California, USA.
Colin Holbrook*Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Clinical Sciences Research Center, Stanford University School of Medicine, Stanford, California, USA; Falk Cardiovascular Research Center, Stanford University School of Medicine, Stanford, California, USA; SpectraCell Laboratories, Inc., Houston, Texas, USA; and Department of Mechanical Engineering, Stanford University, Stanford, California, USA.
Moritz Brandt*Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Clinical Sciences Research Center, Stanford University School of Medicine, Stanford, California, USA; Falk Cardiovascular Research Center, Stanford University School of Medicine, Stanford, California, USA; SpectraCell Laboratories, Inc., Houston, Texas, USA; and Department of Mechanical Engineering, Stanford University, Stanford, California, USA.
Jonathan Stein*Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Clinical Sciences Research Center, Stanford University School of Medicine, Stanford, California, USA; Falk Cardiovascular Research Center, Stanford University School of Medicine, Stanford, California, USA; SpectraCell Laboratories, Inc., Houston, Texas, USA; and Department of Mechanical Engineering, Stanford University, Stanford, California, USA.
Juan G Santiago*Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Clinical Sciences Research Center, Stanford University School of Medicine, Stanford, California, USA; Falk Cardiovascular Research Center, Stanford University School of Medicine, Stanford, California, USA; SpectraCell Laboratories, Inc., Houston, Texas, USA; and Department of Mechanical Engineering, Stanford University, Stanford, California, USA.
John P Cooke*Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Clinical Sciences Research Center, Stanford University School of Medicine, Stanford, California, USA; Falk Cardiovascular Research Center, Stanford University School of Medicine, Stanford, California, USA; SpectraCell Laboratories, Inc., Houston, Texas, USA; and Department of Mechanical Engineering, Stanford University, Stanford, California, USA.
Helen M Blau*Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Clinical Sciences Research Center, Stanford University School of Medicine, Stanford, California, USA; Falk Cardiovascular Research Center, Stanford University School of Medicine, Stanford, California, USA; SpectraCell Laboratories, Inc., Houston, Texas, USA; and Department of Mechanical Engineering, Stanford University, Stanford, California, USA hblau@stanford.edu.
Stanford University · USInstitute for Stem Cell Biology and Regenerative Medicine · INIncell Corporation (United States) · US

Funding

Progenitor Cell Biology Consortium Administrative Coordinating CenterU01HL099997 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI TERRIN, MICHAEL L · 2009 to 2015
$29.9M
Basic and Translational Research iPSC-based hematologic and vascular therapiesU01HL100397 · NHLBI · STANFORD UNIVERSITY · PI COOKE, JOHN P · 2009 to 2015
$7.4M
Telomere extension using nucleoside-modified mRNA and exosomes as a novel therapeR01AR063963 · NIAMS · STANFORD UNIVERSITY · PI BLAU, HELEN M · 2012 to 2016
$4.3M
Role of Non-muscle MLCK in Neutrophil-mediated Acute Lung InjuryR01HL095716 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI XU, JINGSONG · 2009 to 2013
$2.1M
Safe, Rapid Telomere Extension to Prevent and Treat HypertensionR21AG044815 · NIA · STANFORD UNIVERSITY · PI BLAU, HELEN M · 2013 to 2014
$434k
NHLBI NIH HHS R01 HL095716NHLBI NIH HHS U01 HL099997NHLBI NIH HHS U01HL099997NHLBI NIH HHS U01 HL100397NHLBI NIH HHS U01HL100397NIAMS NIH HHS R01 AR063963NIAMS NIH HHS R01AR063963NIA NIH HHS AG044815-01NIA NIH HHS R21 AG044815
6 · The paper itself

Abstract

Telomere extension has been proposed as a means to improve cell culture and tissue engineering and to treat disease. However, telomere extension by nonviral, nonintegrating methods remains inefficient. Here we report that delivery of modified mRNA encoding TERT to human fibroblasts and myoblasts increases telomerase activity transiently (24-48 h) and rapidly extends telomeres, after which telomeres resume shortening. Three successive transfections over a 4 d period extended telomeres up to 0.9 kb in a cell type-specific manner in fibroblasts and myoblasts and conferred an additional 28 ± 1.5 and 3.4 ± 0.4 population doublings (PDs), respectively. Proliferative capacity increased in a dose-dependent manner. The second and third transfections had less effect on proliferative capacity than the first, revealing a refractory period. However, the refractory period was transient as a later fourth transfection increased fibroblast proliferative capacity by an additional 15.2 ± 1.1 PDs, similar to the first transfection. Overall, these treatments led to an increase in absolute cell number of more than 10(12)-fold. Notably, unlike immortalized cells, all treated cell populations eventually stopped increasing in number and expressed senescence markers to the same extent as untreated cells. This rapid method of extending telomeres and increasing cell proliferative capacity without risk of insertional mutagenesis should have broad utility in disease modeling, drug screening, and regenerative medicine.

Indexed as

Blotting, WesternCell DivisionCell ProliferationCells, CulturedCellular SenescenceFetusFibroblastsFlow CytometryHumansImmunoenzyme TechniquesIn Situ Hybridization, FluorescenceLungMyoblastsReal-Time Polymerase Chain ReactionReverse Transcriptase Polymerase Chain ReactionRNA, MessengerRNA, MessengerTelomeraseTERT protein, humannucleoside modified mRNAproliferative capacitysenescencetelomerase

Identifiers

PMID25614443
PMCPMC4415018
OpenAlexW2103428818

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.