Trial reportThe New England journal of medicine2021
Post-Transcriptional Genetic Silencing of
Registry-linked trialOpen access · greenAbstract readClinical Trial
In one paragraph
Trial report in The New England journal of medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03282656 (Pilot and Feasibility Study of Hematopoietic Stem Cell Gene Transfer for Sickle Cell Disease), which is not on this map. Cited by 252 papers, 3 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
252citing papers in PubMed, 3 pooled it
32.4field-weighted citation impact, top 1% of its field
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.
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.
Pilot and Feasibility Study of Hematopoietic Stem Cell Gene Transfer for Sickle Cell Disease
Who cites it
252 citing papers in PubMed, 3 syntheses or guidelines pooled it, 418 citations in OpenAlex.
- Gene Therapy for Sickle Cell Disease: Practice Recommendations from the American Society for Transplantation and Cellular Therapy and the International Society for Cell & Gene Therapy.Transplantation and cellular therapy · 2026Guideline
- Balancing benefits and burdens: a systematic review on ethical and social dimensions of gene and cell therapies for hereditary blood diseases.BMC medical ethics · 2025Pooled it
- Genetic Variation and Sickle Cell Disease Severity: A Systematic Review and Meta-Analysis.JAMA network open · 2023Pooled it
- Clinical outcomes of lentiviral vector gene therapy for sickle cell disease.Blood advances · 2026Trial
- Lentiviral gene therapy with reduced-intensity conditioning for sickle cell disease: a phase 1/2 trial.Nature medicine · 2025Trial
- Incremental eligibility criteria for the BMT CTN 1507 haploidentical trial for children with sickle cell disease.Blood advances · 2024Trial
- Zinc finger nuclease-mediated gene editing in hematopoietic stem cells results in reactivation of fetal hemoglobin in sickle cell disease.Scientific reports · 2024Trial
- Hydroxyurea dose optimisation for children with sickle cell anaemia in sub-Saharan Africa (REACH): extended follow-up of a multicentre, open-label, phase 1/2 trial.The Lancet. Haematology · 2024Trial
- In vivo measurement of RBC survival in patients with sickle cell disease before or after hematopoietic stem cell transplantation.Blood advances · 2024Trial
- CRISPR-Cas9 Editing of theThe New England journal of medicine · 2023Trial
- Significant improvement of child physical and emotional functioning after familial haploidentical stem cell transplant.Bone marrow transplantation · 2022Trial
- Gene therapy for hereditary hematological disorders: From clinical breakthroughs to future horizons.Molecular therapy. Nucleic acids · 2026Review
- Modifying quality and equity of care: emerging roles of genetic disease modifiers in β-hemoglobinopathies.Blood advances · 2026Review
- Systemic delivery of phagocytosis-shielded retroviral vectors enables in vivo HSC gene therapy for sickle cell disease.Cell stem cell · 2026Article
- Article
- Precision base-editing of the cryptic 3' acceptor site to correct the RNA splicing defect of βMolecular biomedicine · 2026Article
- Alternative conditioning regimens for hemoglobinopathy gene therapy: balancing efficacy, toxicity, and the next frontier.Blood advances · 2026Review
- Beyond Precision: A Multidimensional Framework for Selecting Genetic Medicine Platforms.Cells · 2026Review
- Sickle Cell Disease: From Ancient Origins to Modern Breakthroughs in Gene Therapy.Biomedicines · 2026Review
- Circulating erythropoietin concentration associates with thromboembolism in sickle cell disease.British journal of haematology · 2026Article
192 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
25 authors at 5 institutions in 1 country.
Erica B EsrickFrom the Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School (E.B.E., L.E.L., A.B., C.B., M.F.C., B.M., K.B., S.-Y.P., W.B.L., C.D., M.M.H., D.A.W.), the Harvard Stem Cell Institute, Harvard Medical School (A.B., C.B.), the Gene Therapy Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center (A.B., M.F.C., B.M., E.M., A.F., S.-Y.P., C.D., D.A.W.), the Division of Hematology, Brigham and Women's Hospital, Harvard Medical School (M. Achebe), the Connell and O'Reilly Families Cell Manipulation Core Facility, Dana-Farber Cancer Institute (H.D., R.K., K.S., H.N., S.N., J.R.), the TransLab, Boston Children's Hospital (D.A., M. Armant), and the Department of Laboratory Medicine, Boston Children's Hospital, Harvard Medical School (J.P.M.) - all in Boston; and Bluebird Bio, Cambridge, MA (O.N.).
Leslie E LehmannFrom the Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School (E.B.E., L.E.L., A.B., C.B., M.F.C., B.M., K.B., S.-Y.P., W.B.L., C.D., M.M.H., D.A.W.), the Harvard Stem Cell Institute, Harvard Medical School (A.B., C.B.), the Gene Therapy Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center (A.B., M.F.C., B.M., E.M., A.F., S.-Y.P., C.D., D.A.W.), the Division of Hematology, Brigham and Women's Hospital, Harvard Medical School (M. Achebe), the Connell and O'Reilly Families Cell Manipulation Core Facility, Dana-Farber Cancer Institute (H.D., R.K., K.S., H.N., S.N., J.R.), the TransLab, Boston Children's Hospital (D.A., M. Armant), and the Department of Laboratory Medicine, Boston Children's Hospital, Harvard Medical School (J.P.M.) - all in Boston; and Bluebird Bio, Cambridge, MA (O.N.).
Alessandra BiffiFrom the Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School (E.B.E., L.E.L., A.B., C.B., M.F.C., B.M., K.B., S.-Y.P., W.B.L., C.D., M.M.H., D.A.W.), the Harvard Stem Cell Institute, Harvard Medical School (A.B., C.B.), the Gene Therapy Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center (A.B., M.F.C., B.M., E.M., A.F., S.-Y.P., C.D., D.A.W.), the Division of Hematology, Brigham and Women's Hospital, Harvard Medical School (M. Achebe), the Connell and O'Reilly Families Cell Manipulation Core Facility, Dana-Farber Cancer Institute (H.D., R.K., K.S., H.N., S.N., J.R.), the TransLab, Boston Children's Hospital (D.A., M. Armant), and the Department of Laboratory Medicine, Boston Children's Hospital, Harvard Medical School (J.P.M.) - all in Boston; and Bluebird Bio, Cambridge, MA (O.N.).
Maureen AchebeFrom the Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School (E.B.E., L.E.L., A.B., C.B., M.F.C., B.M., K.B., S.-Y.P., W.B.L., C.D., M.M.H., D.A.W.), the Harvard Stem Cell Institute, Harvard Medical School (A.B., C.B.), the Gene Therapy Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center (A.B., M.F.C., B.M., E.M., A.F., S.-Y.P., C.D., D.A.W.), the Division of Hematology, Brigham and Women's Hospital, Harvard Medical School (M. Achebe), the Connell and O'Reilly Families Cell Manipulation Core Facility, Dana-Farber Cancer Institute (H.D., R.K., K.S., H.N., S.N., J.R.), the TransLab, Boston Children's Hospital (D.A., M. Armant), and the Department of Laboratory Medicine, Boston Children's Hospital, Harvard Medical School (J.P.M.) - all in Boston; and Bluebird Bio, Cambridge, MA (O.N.).
Christian BrendelFrom the Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School (E.B.E., L.E.L., A.B., C.B., M.F.C., B.M., K.B., S.-Y.P., W.B.L., C.D., M.M.H., D.A.W.), the Harvard Stem Cell Institute, Harvard Medical School (A.B., C.B.), the Gene Therapy Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center (A.B., M.F.C., B.M., E.M., A.F., S.-Y.P., C.D., D.A.W.), the Division of Hematology, Brigham and Women's Hospital, Harvard Medical School (M. Achebe), the Connell and O'Reilly Families Cell Manipulation Core Facility, Dana-Farber Cancer Institute (H.D., R.K., K.S., H.N., S.N., J.R.), the TransLab, Boston Children's Hospital (D.A., M. Armant), and the Department of Laboratory Medicine, Boston Children's Hospital, Harvard Medical School (J.P.M.) - all in Boston; and Bluebird Bio, Cambridge, MA (O.N.).
Marioara F CiuculescuFrom the Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School (E.B.E., L.E.L., A.B., C.B., M.F.C., B.M., K.B., S.-Y.P., W.B.L., C.D., M.M.H., D.A.W.), the Harvard Stem Cell Institute, Harvard Medical School (A.B., C.B.), the Gene Therapy Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center (A.B., M.F.C., B.M., E.M., A.F., S.-Y.P., C.D., D.A.W.), the Division of Hematology, Brigham and Women's Hospital, Harvard Medical School (M. Achebe), the Connell and O'Reilly Families Cell Manipulation Core Facility, Dana-Farber Cancer Institute (H.D., R.K., K.S., H.N., S.N., J.R.), the TransLab, Boston Children's Hospital (D.A., M. Armant), and the Department of Laboratory Medicine, Boston Children's Hospital, Harvard Medical School (J.P.M.) - all in Boston; and Bluebird Bio, Cambridge, MA (O.N.).
Heather DaleyFrom the Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School (E.B.E., L.E.L., A.B., C.B., M.F.C., B.M., K.B., S.-Y.P., W.B.L., C.D., M.M.H., D.A.W.), the Harvard Stem Cell Institute, Harvard Medical School (A.B., C.B.), the Gene Therapy Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center (A.B., M.F.C., B.M., E.M., A.F., S.-Y.P., C.D., D.A.W.), the Division of Hematology, Brigham and Women's Hospital, Harvard Medical School (M. Achebe), the Connell and O'Reilly Families Cell Manipulation Core Facility, Dana-Farber Cancer Institute (H.D., R.K., K.S., H.N., S.N., J.R.), the TransLab, Boston Children's Hospital (D.A., M. Armant), and the Department of Laboratory Medicine, Boston Children's Hospital, Harvard Medical School (J.P.M.) - all in Boston; and Bluebird Bio, Cambridge, MA (O.N.).
Brenda MacKinnonFrom the Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School (E.B.E., L.E.L., A.B., C.B., M.F.C., B.M., K.B., S.-Y.P., W.B.L., C.D., M.M.H., D.A.W.), the Harvard Stem Cell Institute, Harvard Medical School (A.B., C.B.), the Gene Therapy Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center (A.B., M.F.C., B.M., E.M., A.F., S.-Y.P., C.D., D.A.W.), the Division of Hematology, Brigham and Women's Hospital, Harvard Medical School (M. Achebe), the Connell and O'Reilly Families Cell Manipulation Core Facility, Dana-Farber Cancer Institute (H.D., R.K., K.S., H.N., S.N., J.R.), the TransLab, Boston Children's Hospital (D.A., M. Armant), and the Department of Laboratory Medicine, Boston Children's Hospital, Harvard Medical School (J.P.M.) - all in Boston; and Bluebird Bio, Cambridge, MA (O.N.).
Emily MorrisFrom the Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School (E.B.E., L.E.L., A.B., C.B., M.F.C., B.M., K.B., S.-Y.P., W.B.L., C.D., M.M.H., D.A.W.), the Harvard Stem Cell Institute, Harvard Medical School (A.B., C.B.), the Gene Therapy Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center (A.B., M.F.C., B.M., E.M., A.F., S.-Y.P., C.D., D.A.W.), the Division of Hematology, Brigham and Women's Hospital, Harvard Medical School (M. Achebe), the Connell and O'Reilly Families Cell Manipulation Core Facility, Dana-Farber Cancer Institute (H.D., R.K., K.S., H.N., S.N., J.R.), the TransLab, Boston Children's Hospital (D.A., M. Armant), and the Department of Laboratory Medicine, Boston Children's Hospital, Harvard Medical School (J.P.M.) - all in Boston; and Bluebird Bio, Cambridge, MA (O.N.).
Amy FedericoFrom the Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School (E.B.E., L.E.L., A.B., C.B., M.F.C., B.M., K.B., S.-Y.P., W.B.L., C.D., M.M.H., D.A.W.), the Harvard Stem Cell Institute, Harvard Medical School (A.B., C.B.), the Gene Therapy Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center (A.B., M.F.C., B.M., E.M., A.F., S.-Y.P., C.D., D.A.W.), the Division of Hematology, Brigham and Women's Hospital, Harvard Medical School (M. Achebe), the Connell and O'Reilly Families Cell Manipulation Core Facility, Dana-Farber Cancer Institute (H.D., R.K., K.S., H.N., S.N., J.R.), the TransLab, Boston Children's Hospital (D.A., M. Armant), and the Department of Laboratory Medicine, Boston Children's Hospital, Harvard Medical School (J.P.M.) - all in Boston; and Bluebird Bio, Cambridge, MA (O.N.).
Daniela AbrissFrom the Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School (E.B.E., L.E.L., A.B., C.B., M.F.C., B.M., K.B., S.-Y.P., W.B.L., C.D., M.M.H., D.A.W.), the Harvard Stem Cell Institute, Harvard Medical School (A.B., C.B.), the Gene Therapy Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center (A.B., M.F.C., B.M., E.M., A.F., S.-Y.P., C.D., D.A.W.), the Division of Hematology, Brigham and Women's Hospital, Harvard Medical School (M. Achebe), the Connell and O'Reilly Families Cell Manipulation Core Facility, Dana-Farber Cancer Institute (H.D., R.K., K.S., H.N., S.N., J.R.), the TransLab, Boston Children's Hospital (D.A., M. Armant), and the Department of Laboratory Medicine, Boston Children's Hospital, Harvard Medical School (J.P.M.) - all in Boston; and Bluebird Bio, Cambridge, MA (O.N.).
Kari BoardmanFrom the Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School (E.B.E., L.E.L., A.B., C.B., M.F.C., B.M., K.B., S.-Y.P., W.B.L., C.D., M.M.H., D.A.W.), the Harvard Stem Cell Institute, Harvard Medical School (A.B., C.B.), the Gene Therapy Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center (A.B., M.F.C., B.M., E.M., A.F., S.-Y.P., C.D., D.A.W.), the Division of Hematology, Brigham and Women's Hospital, Harvard Medical School (M. Achebe), the Connell and O'Reilly Families Cell Manipulation Core Facility, Dana-Farber Cancer Institute (H.D., R.K., K.S., H.N., S.N., J.R.), the TransLab, Boston Children's Hospital (D.A., M. Armant), and the Department of Laboratory Medicine, Boston Children's Hospital, Harvard Medical School (J.P.M.) - all in Boston; and Bluebird Bio, Cambridge, MA (O.N.).
Radia KhelladiFrom the Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School (E.B.E., L.E.L., A.B., C.B., M.F.C., B.M., K.B., S.-Y.P., W.B.L., C.D., M.M.H., D.A.W.), the Harvard Stem Cell Institute, Harvard Medical School (A.B., C.B.), the Gene Therapy Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center (A.B., M.F.C., B.M., E.M., A.F., S.-Y.P., C.D., D.A.W.), the Division of Hematology, Brigham and Women's Hospital, Harvard Medical School (M. Achebe), the Connell and O'Reilly Families Cell Manipulation Core Facility, Dana-Farber Cancer Institute (H.D., R.K., K.S., H.N., S.N., J.R.), the TransLab, Boston Children's Hospital (D.A., M. Armant), and the Department of Laboratory Medicine, Boston Children's Hospital, Harvard Medical School (J.P.M.) - all in Boston; and Bluebird Bio, Cambridge, MA (O.N.).
Kit ShawFrom the Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School (E.B.E., L.E.L., A.B., C.B., M.F.C., B.M., K.B., S.-Y.P., W.B.L., C.D., M.M.H., D.A.W.), the Harvard Stem Cell Institute, Harvard Medical School (A.B., C.B.), the Gene Therapy Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center (A.B., M.F.C., B.M., E.M., A.F., S.-Y.P., C.D., D.A.W.), the Division of Hematology, Brigham and Women's Hospital, Harvard Medical School (M. Achebe), the Connell and O'Reilly Families Cell Manipulation Core Facility, Dana-Farber Cancer Institute (H.D., R.K., K.S., H.N., S.N., J.R.), the TransLab, Boston Children's Hospital (D.A., M. Armant), and the Department of Laboratory Medicine, Boston Children's Hospital, Harvard Medical School (J.P.M.) - all in Boston; and Bluebird Bio, Cambridge, MA (O.N.).
Helene NegreFrom the Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School (E.B.E., L.E.L., A.B., C.B., M.F.C., B.M., K.B., S.-Y.P., W.B.L., C.D., M.M.H., D.A.W.), the Harvard Stem Cell Institute, Harvard Medical School (A.B., C.B.), the Gene Therapy Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center (A.B., M.F.C., B.M., E.M., A.F., S.-Y.P., C.D., D.A.W.), the Division of Hematology, Brigham and Women's Hospital, Harvard Medical School (M. Achebe), the Connell and O'Reilly Families Cell Manipulation Core Facility, Dana-Farber Cancer Institute (H.D., R.K., K.S., H.N., S.N., J.R.), the TransLab, Boston Children's Hospital (D.A., M. Armant), and the Department of Laboratory Medicine, Boston Children's Hospital, Harvard Medical School (J.P.M.) - all in Boston; and Bluebird Bio, Cambridge, MA (O.N.).
Olivier NegreFrom the Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School (E.B.E., L.E.L., A.B., C.B., M.F.C., B.M., K.B., S.-Y.P., W.B.L., C.D., M.M.H., D.A.W.), the Harvard Stem Cell Institute, Harvard Medical School (A.B., C.B.), the Gene Therapy Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center (A.B., M.F.C., B.M., E.M., A.F., S.-Y.P., C.D., D.A.W.), the Division of Hematology, Brigham and Women's Hospital, Harvard Medical School (M. Achebe), the Connell and O'Reilly Families Cell Manipulation Core Facility, Dana-Farber Cancer Institute (H.D., R.K., K.S., H.N., S.N., J.R.), the TransLab, Boston Children's Hospital (D.A., M. Armant), and the Department of Laboratory Medicine, Boston Children's Hospital, Harvard Medical School (J.P.M.) - all in Boston; and Bluebird Bio, Cambridge, MA (O.N.).
Sarah NikiforowFrom the Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School (E.B.E., L.E.L., A.B., C.B., M.F.C., B.M., K.B., S.-Y.P., W.B.L., C.D., M.M.H., D.A.W.), the Harvard Stem Cell Institute, Harvard Medical School (A.B., C.B.), the Gene Therapy Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center (A.B., M.F.C., B.M., E.M., A.F., S.-Y.P., C.D., D.A.W.), the Division of Hematology, Brigham and Women's Hospital, Harvard Medical School (M. Achebe), the Connell and O'Reilly Families Cell Manipulation Core Facility, Dana-Farber Cancer Institute (H.D., R.K., K.S., H.N., S.N., J.R.), the TransLab, Boston Children's Hospital (D.A., M. Armant), and the Department of Laboratory Medicine, Boston Children's Hospital, Harvard Medical School (J.P.M.) - all in Boston; and Bluebird Bio, Cambridge, MA (O.N.).
Jerome RitzFrom the Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School (E.B.E., L.E.L., A.B., C.B., M.F.C., B.M., K.B., S.-Y.P., W.B.L., C.D., M.M.H., D.A.W.), the Harvard Stem Cell Institute, Harvard Medical School (A.B., C.B.), the Gene Therapy Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center (A.B., M.F.C., B.M., E.M., A.F., S.-Y.P., C.D., D.A.W.), the Division of Hematology, Brigham and Women's Hospital, Harvard Medical School (M. Achebe), the Connell and O'Reilly Families Cell Manipulation Core Facility, Dana-Farber Cancer Institute (H.D., R.K., K.S., H.N., S.N., J.R.), the TransLab, Boston Children's Hospital (D.A., M. Armant), and the Department of Laboratory Medicine, Boston Children's Hospital, Harvard Medical School (J.P.M.) - all in Boston; and Bluebird Bio, Cambridge, MA (O.N.).
Sung-Yun PaiFrom the Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School (E.B.E., L.E.L., A.B., C.B., M.F.C., B.M., K.B., S.-Y.P., W.B.L., C.D., M.M.H., D.A.W.), the Harvard Stem Cell Institute, Harvard Medical School (A.B., C.B.), the Gene Therapy Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center (A.B., M.F.C., B.M., E.M., A.F., S.-Y.P., C.D., D.A.W.), the Division of Hematology, Brigham and Women's Hospital, Harvard Medical School (M. Achebe), the Connell and O'Reilly Families Cell Manipulation Core Facility, Dana-Farber Cancer Institute (H.D., R.K., K.S., H.N., S.N., J.R.), the TransLab, Boston Children's Hospital (D.A., M. Armant), and the Department of Laboratory Medicine, Boston Children's Hospital, Harvard Medical School (J.P.M.) - all in Boston; and Bluebird Bio, Cambridge, MA (O.N.).
Wendy B LondonFrom the Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School (E.B.E., L.E.L., A.B., C.B., M.F.C., B.M., K.B., S.-Y.P., W.B.L., C.D., M.M.H., D.A.W.), the Harvard Stem Cell Institute, Harvard Medical School (A.B., C.B.), the Gene Therapy Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center (A.B., M.F.C., B.M., E.M., A.F., S.-Y.P., C.D., D.A.W.), the Division of Hematology, Brigham and Women's Hospital, Harvard Medical School (M. Achebe), the Connell and O'Reilly Families Cell Manipulation Core Facility, Dana-Farber Cancer Institute (H.D., R.K., K.S., H.N., S.N., J.R.), the TransLab, Boston Children's Hospital (D.A., M. Armant), and the Department of Laboratory Medicine, Boston Children's Hospital, Harvard Medical School (J.P.M.) - all in Boston; and Bluebird Bio, Cambridge, MA (O.N.).
Colleen DansereauFrom the Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School (E.B.E., L.E.L., A.B., C.B., M.F.C., B.M., K.B., S.-Y.P., W.B.L., C.D., M.M.H., D.A.W.), the Harvard Stem Cell Institute, Harvard Medical School (A.B., C.B.), the Gene Therapy Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center (A.B., M.F.C., B.M., E.M., A.F., S.-Y.P., C.D., D.A.W.), the Division of Hematology, Brigham and Women's Hospital, Harvard Medical School (M. Achebe), the Connell and O'Reilly Families Cell Manipulation Core Facility, Dana-Farber Cancer Institute (H.D., R.K., K.S., H.N., S.N., J.R.), the TransLab, Boston Children's Hospital (D.A., M. Armant), and the Department of Laboratory Medicine, Boston Children's Hospital, Harvard Medical School (J.P.M.) - all in Boston; and Bluebird Bio, Cambridge, MA (O.N.).
Matthew M HeeneyFrom the Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School (E.B.E., L.E.L., A.B., C.B., M.F.C., B.M., K.B., S.-Y.P., W.B.L., C.D., M.M.H., D.A.W.), the Harvard Stem Cell Institute, Harvard Medical School (A.B., C.B.), the Gene Therapy Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center (A.B., M.F.C., B.M., E.M., A.F., S.-Y.P., C.D., D.A.W.), the Division of Hematology, Brigham and Women's Hospital, Harvard Medical School (M. Achebe), the Connell and O'Reilly Families Cell Manipulation Core Facility, Dana-Farber Cancer Institute (H.D., R.K., K.S., H.N., S.N., J.R.), the TransLab, Boston Children's Hospital (D.A., M. Armant), and the Department of Laboratory Medicine, Boston Children's Hospital, Harvard Medical School (J.P.M.) - all in Boston; and Bluebird Bio, Cambridge, MA (O.N.).
Myriam ArmantFrom the Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School (E.B.E., L.E.L., A.B., C.B., M.F.C., B.M., K.B., S.-Y.P., W.B.L., C.D., M.M.H., D.A.W.), the Harvard Stem Cell Institute, Harvard Medical School (A.B., C.B.), the Gene Therapy Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center (A.B., M.F.C., B.M., E.M., A.F., S.-Y.P., C.D., D.A.W.), the Division of Hematology, Brigham and Women's Hospital, Harvard Medical School (M. Achebe), the Connell and O'Reilly Families Cell Manipulation Core Facility, Dana-Farber Cancer Institute (H.D., R.K., K.S., H.N., S.N., J.R.), the TransLab, Boston Children's Hospital (D.A., M. Armant), and the Department of Laboratory Medicine, Boston Children's Hospital, Harvard Medical School (J.P.M.) - all in Boston; and Bluebird Bio, Cambridge, MA (O.N.).
John P ManisFrom the Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School (E.B.E., L.E.L., A.B., C.B., M.F.C., B.M., K.B., S.-Y.P., W.B.L., C.D., M.M.H., D.A.W.), the Harvard Stem Cell Institute, Harvard Medical School (A.B., C.B.), the Gene Therapy Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center (A.B., M.F.C., B.M., E.M., A.F., S.-Y.P., C.D., D.A.W.), the Division of Hematology, Brigham and Women's Hospital, Harvard Medical School (M. Achebe), the Connell and O'Reilly Families Cell Manipulation Core Facility, Dana-Farber Cancer Institute (H.D., R.K., K.S., H.N., S.N., J.R.), the TransLab, Boston Children's Hospital (D.A., M. Armant), and the Department of Laboratory Medicine, Boston Children's Hospital, Harvard Medical School (J.P.M.) - all in Boston; and Bluebird Bio, Cambridge, MA (O.N.).
David A WilliamsFrom the Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School (E.B.E., L.E.L., A.B., C.B., M.F.C., B.M., K.B., S.-Y.P., W.B.L., C.D., M.M.H., D.A.W.), the Harvard Stem Cell Institute, Harvard Medical School (A.B., C.B.), the Gene Therapy Program, Dana-Farber/Boston Children's Cancer and Blood Disorders Center (A.B., M.F.C., B.M., E.M., A.F., S.-Y.P., C.D., D.A.W.), the Division of Hematology, Brigham and Women's Hospital, Harvard Medical School (M. Achebe), the Connell and O'Reilly Families Cell Manipulation Core Facility, Dana-Farber Cancer Institute (H.D., R.K., K.S., H.N., S.N., J.R.), the TransLab, Boston Children's Hospital (D.A., M. Armant), and the Department of Laboratory Medicine, Boston Children's Hospital, Harvard Medical School (J.P.M.) - all in Boston; and Bluebird Bio, Cambridge, MA (O.N.).ORCID 0000-0001-7057-6863
Dana-Farber/Boston Children's Cancer and Blood Disorders Center · USDana-Farber Cancer Institute · USBoston Children's Hospital · USHarvard University · USBrigham and Women's Hospital · US
Funding
PATHOPHYSIOLOGY OF HUMAN BLOOD CELLST32HL007574 · NHLBI · CHILDREN'S HOSPITAL BOSTON · PI Daniel Evan Bauer · 1985 to 2026
$18.4MGene therapy targeting BCL11A to induce fetal hemoglobin and reduce sickle hemoglobin in patients with Sickle Cell DiseaseR01HL137848 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI WILLIAMS, DAVID A · 2017 to 2021
$6.0MNHLBI NIH HHS 5R01HL137848NHLBI NIH HHS NCT03282656NHLBI NIH HHS R01 HL137848NHLBI NIH HHS T32 HL007574
Abstract
backgroundSickle cell disease is characterized by hemolytic anemia, pain, and progressive organ damage. A high level of erythrocyte fetal hemoglobin (HbF) comprising α- and γ-globins may ameliorate these manifestations by mitigating sickle hemoglobin polymerization and erythrocyte sickling.
methodsWe enrolled patients with sickle cell disease in a single-center, open-label pilot study. The investigational therapy involved infusion of autologous CD34+ cells transduced with the BCH-BB694 lentiviral vector, which encodes a short hairpin RNA (shRNA) targeting
resultsAs of October 2020, six patients had been followed for at least 6 months after receiving BCH-BB694 gene therapy; median follow-up was 18 months (range, 7 to 29). All patients had engraftment, and adverse events were consistent with effects of the preparative chemotherapy. All the patients who could be fully evaluated achieved robust and stable HbF induction (percentage HbF/(F+S) at most recent follow-up, 20.4 to 41.3%), with HbF broadly distributed in red cells (F-cells 58.9 to 93.6% of untransfused red cells) and HbF per F-cell of 9.0 to 18.6 pg per cell. Clinical manifestations of sickle cell disease were reduced or absent during the follow-up period.
conclusionsThis study validates BCL11A inhibition as an effective target for HbF induction and provides preliminary evidence that shmiR-based gene knockdown offers a favorable risk-benefit profile in sickle cell disease. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT03282656).
Indexed as
Genetic TherapyRNA InterferenceAdolescentAdultAnemia, Sickle CellChildDown-RegulationFemaleFetal Hemoglobingamma-GlobinsGene Knockdown TechniquesGenetic VectorsHumansMalePilot ProjectsRepressor ProteinsBCL11A protein, humanFetal Hemoglobingamma-GlobinsRepressor ProteinsRNA, Small Interfering
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Registered trials
NCT03282656ClinicalTrials.gov
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.