ArticleCell stem cell2020
Small-Molecule PAPD5 Inhibitors Restore Telomerase Activity in Patient Stem Cells.
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Article in Cell stem cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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62citing papers in PubMed
7.0field-weighted citation impact, top 2% of its field
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Who cites it
62 citing papers in PubMed, 96 citations in OpenAlex.
- Safety, Tolerability, and Pharmacokinetics of the Novel Hepatitis B Virus Expression Inhibitor GST-HG131 in Healthy Chinese Subjects: a First-in-Human Single- and Multiple-Dose Escalation Trial.Antimicrobial agents and chemotherapy · 2022Trial
- The potential of gene therapy to rescue telomeric and extratelomeric defects in X-linked dyskeratosis congenita.Molecular therapy. Advances · 2026Article
- Primer- and template-independent RNA polymerization by terminal nucleotidyltransferase TENT4B.Nucleic acids research · 2026Article
- Telomere-associated non-malignant pulmonary diseases: Pathogenic mechanisms and therapeutic strategies.Acta pharmaceutica Sinica. B · 2026Review
- Therapeutic inhibition of telomeric DNA damage response rescues hematopoietic dysfunction driven by telomere shortening and aging.Nature aging · 2026Article
- Senescence modulated cardiac repair with pluripotent stem cell-derived cardiomyocytes.Stem cell research & therapy · 2026Article
- Saturating variant analysis of TERC redefines the human telomerase reverse transcription mechanism.bioRxiv : the preprint server for biology · 2026Article
- Biogenesis and Regulation of Telomerase during Development and Cancer.Cold Spring Harbor perspectives in biology · 2026Review
- Exosome-mediated decay of unstable long extended precursors of human telomerase RNA is dependent on 5'-cap trimethylation.Genes & development · 2026Article
- Dyskerin dysfunction in cancer development: from telomere dysregulation to immune deficiency.American journal of cancer research · 2026Review
- Established and emerging non-cellular therapies in inherited bone marrow failure syndromes.Frontiers in immunology · 2026Review
- Extension of replicative lifespan by synthetic engineered telomerase RNA in patient induced pluripotent stem cells.Nature biomedical engineering · 2025Article
- Global research trends and prospects related to telomerase within breast cancer: a bibliometric and visual analysis.Discover oncology · 2025Article
- Extracellular vesicles for delivery of functional telomerase.Cell communication and signaling : CCS · 2025Article
- circHERC1-A telomerase activator.Science advances · 2025Article
- Telomere Shortening in Interstitial Lung Disease: Challenges and Promises.The clinical respiratory journal · 2025Review
- ATM-dependent DNA damage response constrains cell growth and drives clonal hematopoiesis in telomere biology disorders.The Journal of clinical investigation · 2025Article
- Mutant huntingtin induces neuronal apoptosis via derepressing the non-canonical poly(A) polymerase PAPD5.Nature communications · 2025Article
- Immunosenescence in Sepsis: Molecular Mechanisms and Potential Therapeutic Targets.Aging and disease · 2025Review
- Telomeropathies in Interstitial Lung Disease and Lung Transplant Recipients.Journal of clinical medicine · 2025Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 11 institutions in 1 country.
Neha NagpalDivision of Hematology/Oncology, Boston Children's Hospital, Boston, MA, USA; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Stem Cell Institute, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Stem Cell Program, Boston Children's Hospital, Boston, MA, USA; Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA; Harvard Initiative in RNA Medicine, Boston, MA, USA.
Jianing WangHarvard Stem Cell Institute, Boston, MA, USA; Brigham Regenerative Medicine Center, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA.
Jing ZengDivision of Hematology/Oncology, Boston Children's Hospital, Boston, MA, USA; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Stem Cell Institute, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Broad Institute, Boston, MA, USA.
Emily LoDepartment of Biomedical Engineering and Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Diane H MoonDivision of Hematology/Oncology, Boston Children's Hospital, Boston, MA, USA; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Stem Cell Institute, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Stem Cell Program, Boston Children's Hospital, Boston, MA, USA; Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA; Harvard Initiative in RNA Medicine, Boston, MA, USA.
Kevin LukDepartment of Molecular, Cell and Cancer Biology, Li Weibo Institute for Rare Diseases Research, University of Massachusetts Medical School, Worcester, MA, USA.
Roman O BraunDivision of Hematology/Oncology, Boston Children's Hospital, Boston, MA, USA; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Stem Cell Institute, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Stem Cell Program, Boston Children's Hospital, Boston, MA, USA; Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA; Harvard Initiative in RNA Medicine, Boston, MA, USA.
Lauri M BurroughsFred Hutchinson Cancer Research Center, Seattle, WA, USA; Seattle Children's Hospital, Seattle, WA, USA; Department of Pediatrics, University of Washington, Seattle, WA, USA.
Sioban B KeelDivision of Hematology, Department of Medicine, University of Washington, Seattle, WA, USA.
Christopher ReillyDepartment of Medical Oncology, Division of Hematological Malignancies, Dana-Farber Cancer Institute, Boston, MA, USA.
R Coleman LindsleyDepartment of Medical Oncology, Division of Hematological Malignancies, Dana-Farber Cancer Institute, Boston, MA, USA.
Scot A WolfeDepartment of Molecular, Cell and Cancer Biology, Li Weibo Institute for Rare Diseases Research, University of Massachusetts Medical School, Worcester, MA, USA.
Albert K TaiDepartment of Immunology, Tufts University School of Medicine, Boston, MA, USA.
Patrick CahanDepartment of Biomedical Engineering and Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Daniel E BauerDivision of Hematology/Oncology, Boston Children's Hospital, Boston, MA, USA; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Stem Cell Institute, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Broad Institute, Boston, MA, USA.
Yick W FongHarvard Stem Cell Institute, Boston, MA, USA; Brigham Regenerative Medicine Center, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA.
Suneet AgarwalDivision of Hematology/Oncology, Boston Children's Hospital, Boston, MA, USA; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Stem Cell Institute, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Stem Cell Program, Boston Children's Hospital, Boston, MA, USA; Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA; Harvard Initiative in RNA Medicine, Boston, MA, USA. Electronic address: suneet.agarwal@childrens.harvard.edu.
Dana-Farber Cancer Institute · USHarvard Affiliated Emergency Medicine Residency · USHarvard Stem Cell Institute · USUniversity of Massachusetts Chan Medical School · USUniversity of Washington · USBoston Children's Hospital · USBrigham and Women's Hospital · USHarvard University · USJohns Hopkins Medicine · USJohns Hopkins University · USTufts University · US
Funding
TRANSCRIPTION FACTOR GATA-1 IN TERMINAL ERYTHROID DEVELOPMENTP01HL032262 · NHLBI · CHILDREN'S HOSPITAL BOSTON · PI YIEN, YVETTE Y · 1985 to 2021
$38.9MStem Cell and Transplantation BiologyU54DK106829 · NIDDK · FRED HUTCHINSON CANCER RESEARCH CENTER · PI DEREK L STIREWALT · 2015 to 2026
$9.1MTranslational Studies of Inherited Marrow Failure and Myelodysplastic SyndromesR24DK099808 · NIDDK · FRED HUTCHINSON CANCER RESEARCH CENTER · PI ABKOWITZ, JANIS L, EBERT, BENJAMIN LEVINE · 2013 to 2017
$8.2MTraining Program in Molecular HematologyT32HL116324 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI NANCY BERLINER · 2013 to 2026
$7.4MNext-generation antisense therapeutics for ALS and frontotemporal dementiaR01NS111990 · NINDS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Robert H Brown, Jonathan K Watts · 2019 to 2026
$5.2MRegulation of the telomerase RNA component in hematopoiesisR01DK107716 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI SUNEET AGARWAL · 2016 to 2026
$5.0MNext generation hybrid nucleases for precise excision of latent HIV-1 provirusR01AI117839 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI LUBAN, JEREMY, WOLFE, SCOT A · 2015 to 2019
$4.6MFrom intra to intercellular regulatory networks that define cell type identityR35GM124725 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI Patrick Cahan · 2017 to 2026
$4.5MRectifying splicing mutations in blood disorders by gene editingR01HL150669 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI BAUER, DANIEL EVAN, WOLFE, SCOT A · 2020 to 2023
$3.5MGene editing ELANE to understand and treat severe congenital neutropeniaR01HL150553 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI BAUER, DANIEL EVAN, NEWBURGER, PETER E · 2020 to 2023
$3.0MHigh-throughput discovery of essential noncoding sequences for erythropoiesisDP2HL137300 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI BAUER, DANIEL EVAN · 2016 to 2016
$2.7MEnhancing CRISPR Gene Editing in Somatic Tissues by Chemical Modification of Guides and DonorsUG3TR002668 · NCATS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI KHVOROVA, ANASTASIA, SONTHEIMER, ERIK J. · 2018 to 2020
$2.5MNCATS NIH HHS UG3 TR002668NHLBI NIH HHS DP2 HL137300NHLBI NIH HHS F31 HL147482NHLBI NIH HHS P01 HL032262NHLBI NIH HHS R01 HL125527NHLBI NIH HHS R01 HL150553NHLBI NIH HHS R01 HL150669NHLBI NIH HHS T32 HL116324NIAID NIH HHS R01 AI117839NIDDK NIH HHS R01 DK107716NIDDK NIH HHS R24 DK099808NIDDK NIH HHS U54 DK106829NIGMS NIH HHS R01 GM115911NIGMS NIH HHS R35 GM124725NINDS NIH HHS R01 NS111990
Abstract
Genetic lesions that reduce telomerase activity inhibit stem cell replication and cause a range of incurable diseases, including dyskeratosis congenita (DC) and pulmonary fibrosis (PF). Modalities to restore telomerase in stem cells throughout the body remain unclear. Here, we describe small-molecule PAPD5 inhibitors that demonstrate telomere restoration in vitro, in stem cell models, and in vivo. PAPD5 is a non-canonical polymerase that oligoadenylates and destabilizes telomerase RNA component (TERC). We identified BCH001, a specific PAPD5 inhibitor that restored telomerase activity and telomere length in DC patient induced pluripotent stem cells. When human blood stem cells engineered to carry DC-causing PARN mutations were xenotransplanted into immunodeficient mice, oral treatment with a repurposed PAPD5 inhibitor, the dihydroquinolizinone RG7834, rescued TERC 3' end maturation and telomere length. These findings pave the way for developing systemic telomere therapeutics to counteract stem cell exhaustion in DC, PF, and possibly other aging-related diseases.
Indexed as
Dyskeratosis CongenitaInduced Pluripotent Stem CellsTelomeraseAnimalsHumansMiceMutationRNATelomereRNATelomerasedihydroquinolizinonehigh throughput screenPAPD5PARNRG7834telomerasetelomeresTENT4BTERCxenotransplantation
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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.