Trial reportThe New England journal of medicine2023
CRISPR-Cas9 Editing of the
Open access · greenAbstract readClinical Trial, Phase IClinical Trial, Phase IIMulticenter Study
In one paragraph
Trial report in The New England journal of medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
107citing papers in PubMed, 2 pooled it
40.3field-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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
107 citing papers in PubMed, 2 syntheses or guidelines pooled it, 140 citations in OpenAlex.
- CRISPR/Cas9 System as a Promising Therapy in Thalassemia and Sickle Cell Disease: A Systematic Review of Clinical Trials.Molecular biotechnology · 2026Pooled it
- Mandibular Radiographic Assessment in Sickle Cell Disease: A Systematic Review of Radiomorphometric Indices and Fractal Dimension.Special care in dentistry : official publication of the American Association of Hospital Dentists, the Academy of Dentistry for the Handicapped, and the American Society for Geriatric DentistryPooled it
- Lentiviral gene therapy with reduced-intensity conditioning for sickle cell disease: a phase 1/2 trial.Nature medicine · 2025Trial
- Gene therapy for hereditary hematological disorders: From clinical breakthroughs to future horizons.Molecular therapy. Nucleic acids · 2026Review
- Blood rheology after allogeneic hematopoietic stem cell transplantation or gene therapy in sickle cell disease.Blood advances · 2026Article
- Alternative conditioning regimens for hemoglobinopathy gene therapy: balancing efficacy, toxicity, and the next frontier.Blood advances · 2026Review
- Recent Advances in CRISPR/Cas Technologies for Biological Discovery, Therapeutics, and Diagnostics.Biomolecules · 2026Review
- UCA1 lncRNA regulates γ-globin expression by modulating the miR-148b/BCL11A axis.Life science alliance · 2026Article
- Single-cell and in vivo profiling reveal heterogeneous and organ-specific CRISPR-Cas9 off-target and translocation outcomes.Nature communications · 2026Article
- CRISPR application in hematological disorders: from bench to bedside.Blood advances · 2026Review
- Oligopeptides/DNA Coacervate Droplets as Macromolecular Delivery Microcarriers.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Safety considerations of gene-based therapies for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Arrayed dual-gRNA CRISPR screening platform forMolecular therapy. Advances · 2026Article
- Genotoxicity profiling reveals distinct platform-and cell type-specific effects in therapeutic gene editing for genetic hyperinflammation.Cell stem cell · 2026Article
- G-CSF for Mobilizing CD34American journal of hematology · 2026Article
- From mechanism to medicine: CRISPR‒Cas9 delivery strategies, therapeutic applications and translation challenges.Discover nano · 2026Review
- Optimized lentivirus-derived virus-like particles for efficient delivery of Cas9-based genome editors.Nucleic acids research · 2026Article
- Article
- Discontinued therapies for sickle cell disease: status and future directions.Expert opinion on investigational drugs · 2026Review
- DNA and RNA editing for the therapy of human diseases: current status, challenges, and future prospects.Molecular biomedicine · 2026Review
47 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 2 institutions in 3 countries.
Akshay SharmaFrom St. Jude Children's Research Hospital, Memphis, TN (A.S., J.S.H., Y.Z.); Memorial Sloan Kettering Cancer Center, New York (J.-J.B., M.C.); the Novartis Institutes for BioMedical Research, Cambridge, MA (P.B., M.A., A.L., X.Z., S.C., T.M., Y.Y., Y.L., J.Y., V.W.C.Y., S.C.S., S.D.V.); University of Chicago Medicine, Chicago (R.P., J.L.L.); Children's Hospital Los Angeles, Los Angeles (N.K.); IRCCS San Raffaele Hospital, Milan (F.C.); and the Novartis Institutes for BioMedical Research, Basel, Switzerland (U.N.).ORCID 0000-0003-3281-2081
Jaap-Jan BoelensFrom St. Jude Children's Research Hospital, Memphis, TN (A.S., J.S.H., Y.Z.); Memorial Sloan Kettering Cancer Center, New York (J.-J.B., M.C.); the Novartis Institutes for BioMedical Research, Cambridge, MA (P.B., M.A., A.L., X.Z., S.C., T.M., Y.Y., Y.L., J.Y., V.W.C.Y., S.C.S., S.D.V.); University of Chicago Medicine, Chicago (R.P., J.L.L.); Children's Hospital Los Angeles, Los Angeles (N.K.); IRCCS San Raffaele Hospital, Milan (F.C.); and the Novartis Institutes for BioMedical Research, Basel, Switzerland (U.N.).ORCID 0000-0003-2232-6952
Maria CancioFrom St. Jude Children's Research Hospital, Memphis, TN (A.S., J.S.H., Y.Z.); Memorial Sloan Kettering Cancer Center, New York (J.-J.B., M.C.); the Novartis Institutes for BioMedical Research, Cambridge, MA (P.B., M.A., A.L., X.Z., S.C., T.M., Y.Y., Y.L., J.Y., V.W.C.Y., S.C.S., S.D.V.); University of Chicago Medicine, Chicago (R.P., J.L.L.); Children's Hospital Los Angeles, Los Angeles (N.K.); IRCCS San Raffaele Hospital, Milan (F.C.); and the Novartis Institutes for BioMedical Research, Basel, Switzerland (U.N.).
Jane S HankinsFrom St. Jude Children's Research Hospital, Memphis, TN (A.S., J.S.H., Y.Z.); Memorial Sloan Kettering Cancer Center, New York (J.-J.B., M.C.); the Novartis Institutes for BioMedical Research, Cambridge, MA (P.B., M.A., A.L., X.Z., S.C., T.M., Y.Y., Y.L., J.Y., V.W.C.Y., S.C.S., S.D.V.); University of Chicago Medicine, Chicago (R.P., J.L.L.); Children's Hospital Los Angeles, Los Angeles (N.K.); IRCCS San Raffaele Hospital, Milan (F.C.); and the Novartis Institutes for BioMedical Research, Basel, Switzerland (U.N.).
Prafulla BhadFrom St. Jude Children's Research Hospital, Memphis, TN (A.S., J.S.H., Y.Z.); Memorial Sloan Kettering Cancer Center, New York (J.-J.B., M.C.); the Novartis Institutes for BioMedical Research, Cambridge, MA (P.B., M.A., A.L., X.Z., S.C., T.M., Y.Y., Y.L., J.Y., V.W.C.Y., S.C.S., S.D.V.); University of Chicago Medicine, Chicago (R.P., J.L.L.); Children's Hospital Los Angeles, Los Angeles (N.K.); IRCCS San Raffaele Hospital, Milan (F.C.); and the Novartis Institutes for BioMedical Research, Basel, Switzerland (U.N.).
Marjohn AzizyFrom St. Jude Children's Research Hospital, Memphis, TN (A.S., J.S.H., Y.Z.); Memorial Sloan Kettering Cancer Center, New York (J.-J.B., M.C.); the Novartis Institutes for BioMedical Research, Cambridge, MA (P.B., M.A., A.L., X.Z., S.C., T.M., Y.Y., Y.L., J.Y., V.W.C.Y., S.C.S., S.D.V.); University of Chicago Medicine, Chicago (R.P., J.L.L.); Children's Hospital Los Angeles, Los Angeles (N.K.); IRCCS San Raffaele Hospital, Milan (F.C.); and the Novartis Institutes for BioMedical Research, Basel, Switzerland (U.N.).
Andrew LewandowskiFrom St. Jude Children's Research Hospital, Memphis, TN (A.S., J.S.H., Y.Z.); Memorial Sloan Kettering Cancer Center, New York (J.-J.B., M.C.); the Novartis Institutes for BioMedical Research, Cambridge, MA (P.B., M.A., A.L., X.Z., S.C., T.M., Y.Y., Y.L., J.Y., V.W.C.Y., S.C.S., S.D.V.); University of Chicago Medicine, Chicago (R.P., J.L.L.); Children's Hospital Los Angeles, Los Angeles (N.K.); IRCCS San Raffaele Hospital, Milan (F.C.); and the Novartis Institutes for BioMedical Research, Basel, Switzerland (U.N.).
Xiaojun ZhaoFrom St. Jude Children's Research Hospital, Memphis, TN (A.S., J.S.H., Y.Z.); Memorial Sloan Kettering Cancer Center, New York (J.-J.B., M.C.); the Novartis Institutes for BioMedical Research, Cambridge, MA (P.B., M.A., A.L., X.Z., S.C., T.M., Y.Y., Y.L., J.Y., V.W.C.Y., S.C.S., S.D.V.); University of Chicago Medicine, Chicago (R.P., J.L.L.); Children's Hospital Los Angeles, Los Angeles (N.K.); IRCCS San Raffaele Hospital, Milan (F.C.); and the Novartis Institutes for BioMedical Research, Basel, Switzerland (U.N.).
Shripad ChitnisFrom St. Jude Children's Research Hospital, Memphis, TN (A.S., J.S.H., Y.Z.); Memorial Sloan Kettering Cancer Center, New York (J.-J.B., M.C.); the Novartis Institutes for BioMedical Research, Cambridge, MA (P.B., M.A., A.L., X.Z., S.C., T.M., Y.Y., Y.L., J.Y., V.W.C.Y., S.C.S., S.D.V.); University of Chicago Medicine, Chicago (R.P., J.L.L.); Children's Hospital Los Angeles, Los Angeles (N.K.); IRCCS San Raffaele Hospital, Milan (F.C.); and the Novartis Institutes for BioMedical Research, Basel, Switzerland (U.N.).
Radhika PeddintiFrom St. Jude Children's Research Hospital, Memphis, TN (A.S., J.S.H., Y.Z.); Memorial Sloan Kettering Cancer Center, New York (J.-J.B., M.C.); the Novartis Institutes for BioMedical Research, Cambridge, MA (P.B., M.A., A.L., X.Z., S.C., T.M., Y.Y., Y.L., J.Y., V.W.C.Y., S.C.S., S.D.V.); University of Chicago Medicine, Chicago (R.P., J.L.L.); Children's Hospital Los Angeles, Los Angeles (N.K.); IRCCS San Raffaele Hospital, Milan (F.C.); and the Novartis Institutes for BioMedical Research, Basel, Switzerland (U.N.).
Yan ZhengFrom St. Jude Children's Research Hospital, Memphis, TN (A.S., J.S.H., Y.Z.); Memorial Sloan Kettering Cancer Center, New York (J.-J.B., M.C.); the Novartis Institutes for BioMedical Research, Cambridge, MA (P.B., M.A., A.L., X.Z., S.C., T.M., Y.Y., Y.L., J.Y., V.W.C.Y., S.C.S., S.D.V.); University of Chicago Medicine, Chicago (R.P., J.L.L.); Children's Hospital Los Angeles, Los Angeles (N.K.); IRCCS San Raffaele Hospital, Milan (F.C.); and the Novartis Institutes for BioMedical Research, Basel, Switzerland (U.N.).
Neena KapoorFrom St. Jude Children's Research Hospital, Memphis, TN (A.S., J.S.H., Y.Z.); Memorial Sloan Kettering Cancer Center, New York (J.-J.B., M.C.); the Novartis Institutes for BioMedical Research, Cambridge, MA (P.B., M.A., A.L., X.Z., S.C., T.M., Y.Y., Y.L., J.Y., V.W.C.Y., S.C.S., S.D.V.); University of Chicago Medicine, Chicago (R.P., J.L.L.); Children's Hospital Los Angeles, Los Angeles (N.K.); IRCCS San Raffaele Hospital, Milan (F.C.); and the Novartis Institutes for BioMedical Research, Basel, Switzerland (U.N.).
Fabio CiceriFrom St. Jude Children's Research Hospital, Memphis, TN (A.S., J.S.H., Y.Z.); Memorial Sloan Kettering Cancer Center, New York (J.-J.B., M.C.); the Novartis Institutes for BioMedical Research, Cambridge, MA (P.B., M.A., A.L., X.Z., S.C., T.M., Y.Y., Y.L., J.Y., V.W.C.Y., S.C.S., S.D.V.); University of Chicago Medicine, Chicago (R.P., J.L.L.); Children's Hospital Los Angeles, Los Angeles (N.K.); IRCCS San Raffaele Hospital, Milan (F.C.); and the Novartis Institutes for BioMedical Research, Basel, Switzerland (U.N.).
Timothy MaclachlanFrom St. Jude Children's Research Hospital, Memphis, TN (A.S., J.S.H., Y.Z.); Memorial Sloan Kettering Cancer Center, New York (J.-J.B., M.C.); the Novartis Institutes for BioMedical Research, Cambridge, MA (P.B., M.A., A.L., X.Z., S.C., T.M., Y.Y., Y.L., J.Y., V.W.C.Y., S.C.S., S.D.V.); University of Chicago Medicine, Chicago (R.P., J.L.L.); Children's Hospital Los Angeles, Los Angeles (N.K.); IRCCS San Raffaele Hospital, Milan (F.C.); and the Novartis Institutes for BioMedical Research, Basel, Switzerland (U.N.).
Yi YangFrom St. Jude Children's Research Hospital, Memphis, TN (A.S., J.S.H., Y.Z.); Memorial Sloan Kettering Cancer Center, New York (J.-J.B., M.C.); the Novartis Institutes for BioMedical Research, Cambridge, MA (P.B., M.A., A.L., X.Z., S.C., T.M., Y.Y., Y.L., J.Y., V.W.C.Y., S.C.S., S.D.V.); University of Chicago Medicine, Chicago (R.P., J.L.L.); Children's Hospital Los Angeles, Los Angeles (N.K.); IRCCS San Raffaele Hospital, Milan (F.C.); and the Novartis Institutes for BioMedical Research, Basel, Switzerland (U.N.).
Yi LiuFrom St. Jude Children's Research Hospital, Memphis, TN (A.S., J.S.H., Y.Z.); Memorial Sloan Kettering Cancer Center, New York (J.-J.B., M.C.); the Novartis Institutes for BioMedical Research, Cambridge, MA (P.B., M.A., A.L., X.Z., S.C., T.M., Y.Y., Y.L., J.Y., V.W.C.Y., S.C.S., S.D.V.); University of Chicago Medicine, Chicago (R.P., J.L.L.); Children's Hospital Los Angeles, Los Angeles (N.K.); IRCCS San Raffaele Hospital, Milan (F.C.); and the Novartis Institutes for BioMedical Research, Basel, Switzerland (U.N.).
Jianping YuanFrom St. Jude Children's Research Hospital, Memphis, TN (A.S., J.S.H., Y.Z.); Memorial Sloan Kettering Cancer Center, New York (J.-J.B., M.C.); the Novartis Institutes for BioMedical Research, Cambridge, MA (P.B., M.A., A.L., X.Z., S.C., T.M., Y.Y., Y.L., J.Y., V.W.C.Y., S.C.S., S.D.V.); University of Chicago Medicine, Chicago (R.P., J.L.L.); Children's Hospital Los Angeles, Los Angeles (N.K.); IRCCS San Raffaele Hospital, Milan (F.C.); and the Novartis Institutes for BioMedical Research, Basel, Switzerland (U.N.).
Ulrike NaumannFrom St. Jude Children's Research Hospital, Memphis, TN (A.S., J.S.H., Y.Z.); Memorial Sloan Kettering Cancer Center, New York (J.-J.B., M.C.); the Novartis Institutes for BioMedical Research, Cambridge, MA (P.B., M.A., A.L., X.Z., S.C., T.M., Y.Y., Y.L., J.Y., V.W.C.Y., S.C.S., S.D.V.); University of Chicago Medicine, Chicago (R.P., J.L.L.); Children's Hospital Los Angeles, Los Angeles (N.K.); IRCCS San Raffaele Hospital, Milan (F.C.); and the Novartis Institutes for BioMedical Research, Basel, Switzerland (U.N.).
Vionnie W C YuFrom St. Jude Children's Research Hospital, Memphis, TN (A.S., J.S.H., Y.Z.); Memorial Sloan Kettering Cancer Center, New York (J.-J.B., M.C.); the Novartis Institutes for BioMedical Research, Cambridge, MA (P.B., M.A., A.L., X.Z., S.C., T.M., Y.Y., Y.L., J.Y., V.W.C.Y., S.C.S., S.D.V.); University of Chicago Medicine, Chicago (R.P., J.L.L.); Children's Hospital Los Angeles, Los Angeles (N.K.); IRCCS San Raffaele Hospital, Milan (F.C.); and the Novartis Institutes for BioMedical Research, Basel, Switzerland (U.N.).
Susan C StevensonFrom St. Jude Children's Research Hospital, Memphis, TN (A.S., J.S.H., Y.Z.); Memorial Sloan Kettering Cancer Center, New York (J.-J.B., M.C.); the Novartis Institutes for BioMedical Research, Cambridge, MA (P.B., M.A., A.L., X.Z., S.C., T.M., Y.Y., Y.L., J.Y., V.W.C.Y., S.C.S., S.D.V.); University of Chicago Medicine, Chicago (R.P., J.L.L.); Children's Hospital Los Angeles, Los Angeles (N.K.); IRCCS San Raffaele Hospital, Milan (F.C.); and the Novartis Institutes for BioMedical Research, Basel, Switzerland (U.N.).
Serena De VitaFrom St. Jude Children's Research Hospital, Memphis, TN (A.S., J.S.H., Y.Z.); Memorial Sloan Kettering Cancer Center, New York (J.-J.B., M.C.); the Novartis Institutes for BioMedical Research, Cambridge, MA (P.B., M.A., A.L., X.Z., S.C., T.M., Y.Y., Y.L., J.Y., V.W.C.Y., S.C.S., S.D.V.); University of Chicago Medicine, Chicago (R.P., J.L.L.); Children's Hospital Los Angeles, Los Angeles (N.K.); IRCCS San Raffaele Hospital, Milan (F.C.); and the Novartis Institutes for BioMedical Research, Basel, Switzerland (U.N.).
James L LaBelleFrom St. Jude Children's Research Hospital, Memphis, TN (A.S., J.S.H., Y.Z.); Memorial Sloan Kettering Cancer Center, New York (J.-J.B., M.C.); the Novartis Institutes for BioMedical Research, Cambridge, MA (P.B., M.A., A.L., X.Z., S.C., T.M., Y.Y., Y.L., J.Y., V.W.C.Y., S.C.S., S.D.V.); University of Chicago Medicine, Chicago (R.P., J.L.L.); Children's Hospital Los Angeles, Los Angeles (N.K.); IRCCS San Raffaele Hospital, Milan (F.C.); and the Novartis Institutes for BioMedical Research, Basel, Switzerland (U.N.).
St. Jude Children's Research Hospital · USNovartis (Switzerland) · CH
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4MNCI NIH HHS P30 CA008748
Abstract
backgroundSickle cell disease is caused by a defect in the β-globin subunit of adult hemoglobin. Sickle hemoglobin polymerizes under hypoxic conditions, producing deformed red cells that hemolyze and cause vaso-occlusion that results in progressive organ damage and early death. Elevated fetal hemoglobin levels in red cells protect against complications of sickle cell disease. OTQ923, a clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9-edited CD34+ hematopoietic stem- and progenitor-cell (HSPC) product, has a targeted disruption of the
methodsWe performed a tiling CRISPR-Cas9 screen of the
resultsIn preclinical experiments, CD34+ HSPCs (obtained from healthy donors and persons with sickle cell disease) edited with CRISPR-Cas9 and gRNA-68 had sustained on-target editing with no off-target mutations and produced high levels of fetal hemoglobin after in vitro differentiation or xenotransplantation into immunodeficient mice. In the study, three participants received autologous OTQ923 after myeloablative conditioning and were followed for 6 to 18 months. At the end of the follow-up period, all the participants had engraftment and stable induction of fetal hemoglobin (fetal hemoglobin as a percentage of total hemoglobin, 19.0 to 26.8%), with fetal hemoglobin broadly distributed in red cells (F cells as a percentage of red cells, 69.7 to 87.8%). Manifestations of sickle cell disease decreased during the follow-up period.
conclusionsCRISPR-Cas9 disruption of the
Indexed as
Anemia, Sickle CellCRISPR-Cas SystemsErythrocytesFetal HemoglobinHematopoietic Stem Cell TransplantationAnimalsAntigens, CD34Hemoglobin, SickleHumansMicePromoter Regions, GeneticAntigens, CD34Fetal HemoglobinHemoglobin, Sickle
Identifiers
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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.