The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index; 21 of the 28 sources its claims cite were checked for support.
CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia
Open accessAbstract
Summ a r yTransfusion-dependent β-thalassemia (TDT) and sickle cell disease (SCD) are severe monogenic diseases with severe and potentially life-threatening manifestations.BCL11A is a transcription factor that represses γ-globin expression and fetal hemoglobin in erythroid cells.We performed electroporation of CD34+ hematopoietic stem and progenitor cells obtained from healthy donors, with CRISPR-Cas9 targeting the BCL11A erythroid-specific enhancer.Approximately 80% of the alleles at this locus were modified, with no evidence of off-target editing.After undergoing myeloablation, two patients -one with TDT and the other with SCD -received autologous CD34+ cells edited with CRISPR-Cas9 targeting the same BCL11A enhancer.More than a year later, both patients had high levels of allelic editing in bone marrow and blood, increases in fetal hemoglobin that were distributed pancellularly, transfusion independence, and (in the patient with SCD) elimination of vaso-occlusive episodes.(Funded by CRISPR Therapeutics and Vertex Pharmaceuticals; ClinicalTrials.govnumbers, NCT03655678 for CLIMB THAL-111 and NCT03745287 for CLIMB SCD-121.)T ransfusion-dependent β-thalassemia (TDT) and sickle cell disease (SCD) are the most common monogenic diseases worldwide, with an annual diagnosis in approximately 60,000 patients with TDT and 300,000 patients with SCD.[1][2][3] Both diseases are caused by mutations in the hemoglobin β subunit gene (HBB).Mutations in HBB that cause TDT 4 result in reduced (β + ) or absent (β 0 ) β-globin synthesis and an imbalance between the α-like and β-like globin (e.g., β, γ, and δ) chains of hemoglobin, which causes ineffective erythropoiesis.5,6 Sickle hemoglobin is the result of a point mutation in HBB that replaces glutamic acid with valine at amino acid position 6.Polymerization of deoxygenated sickle hemoglobin causes erythrocyte deformation, hemolysis, anemia, painful vaso-occlusive episodes, irreversible end-organ damage, and a reduced life expectancy.5 Treatment options primarily consist of transfusion and iron chelation in patients with TDT 7 and pain management, transfusion, and hydroxyurea in those with SCD. 8 Recently approved therapies, including luspatercept 9 and crizanlizumab, 10 have reduced transfusion requirements in patients with TDT and the incidence of vaso-occlusive episodes in those with SCD, respectively, but neither treatment addresses the underlying cause of the disease nor fully ameliorates disease manifestations.Allogeneic bone marrow transplantation can cure both TDT and CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia
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Claims the paper makes
21 of 28 cited sources checked · 12 supported · 0 flagged · accuracy not yet measured
Every source the paper cites for this claim was checked and supports it.
In the paper
“Genomewide association studies have identified single-nucleotide polymorphisms (SNPs) associated with increased expression of fetal hemoglobin in adults.26”
What the sources say
- Supportedcites [26] 26. Bauer DE, Kamran SC, Lessard S, et al. An erythroid enhancer of BCL11A subject to genetic variation determines fetal hemo- globin level. Science 2013; 342: 253-7. source
The paper states that GWAS identified variants at BCL11A associated with fetal hemoglobin (HbF) level. It also reports a common variant associated with elevated HbF, supporting the citing sentence’s summary (Abstract; page not provided). (LLM, conf=0.88)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Patients with TDT or SCD who co-inherit hereditary persistence of fetal hemoglobin, in which fetal expression continues into adulthood, have little or no disease.25”
What the sources say
- Partly supportedcites [25] 25. Steinberg MH. Fetal hemoglobin in sickle cell anemia. Blood 2020; 136: 2392- 400. sourceExperimental — accuracy not yet measured
The “F-cells: heterogeneity of HbF concentrations” section reports that people with HbS-HPFH usually have no symptoms or hemolytic anemia, supporting the SCD part of the claim. It does not establish the same outcome for patients with transfusion-dependent thalassemia (TDT), so the claim extends beyond the source. (LLM, conf=0.88)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Recently approved therapies, including luspatercept 9 and crizanlizumab, 10 have reduced transfusion requirements in patients with TDT and the incidence of vaso-occlusive episodes in those with SCD, respectively, but neither treatment addresses the underlying cause of the disease nor fully ameliorates disease manifestations.”
What the sources say
- Supportedcites [10] 10. Ataga KI, Kutlar A, Kanter J, et al. Crizanlizumab for the prevention of pain crises in sickle cell disease. N Engl J Med 2017; 376: 429-39. source
The Discussion reports a significantly lower frequency of sickle cell–related pain crises with crizanlizumab than with placebo in patients with SCD. This supports the attributed reduction in vaso-occlusive episodes; the cited paper reports the benefit for high-dose crizanlizumab. (LLM, conf=0.93)
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Some of these SNPs are located in the BCL11A locus on chromosome 2 and are associated with a lower severity of both TDT and SCD.27”
What the sources say
- Partly supportedcites [27] 27. Uda M, Galanello R, Sanna S, et al. Genome-wide association study shows BCL11A associated with persistent fetal hemoglobin and amelioration of the phe- notype of β-thalassemia. Proc Natl Acad Sci U S A 2008; 105: 1620-5. sourceExperimental — accuracy not yet measured
The Results (page unavailable) place rs11886868 in BCL11A on chromosome 2 and find its C allele more frequent in milder, largely non-transfusion-dependent thalassemia intermedia than in transfusion-dependent thalassemia major. For SCD, the Discussion (page unavailable) reports an association with HbF levels, but says that using the variant to predict disease severity requires future study. The paper therefore does not establish lower severity within TDT or SCD. (LLM, conf=0.88)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“BCL11A is a transcription factor that represses γ-globin expression and fetal hemoglobin in erythroid cells.”
What the sources say
- Supportedcites [1] 1. Bauer DE, Orkin SH. Hemoglobin switching's surprise: the versatile tran- scription factor BCL11A is a master re- pressor of fetal hemoglobin. Curr Opin Genet Dev 2015; 33: 62-70. source
The Genetic evidence connecting BCL11A and HbF regulation section identifies BCL11A as a transcriptional repressor and reports that its knockdown in human erythroid precursors leads to fetal hemoglobin expression. It also describes BCL11A's repression of γ-globin; the claim does not imply that BCL11A binds the γ-globin genes directly. (LLM, conf=0.94)
- Supportedcites [23] 23. Sankaran VG, Orkin SH. The switch from fetal to adult hemoglobin. Cold Spring Harb Perspect Med 2013; 3(1): a011643. source
In “Early Molecular Studies Lead to Therapeutic Approaches for HbF Induction,” the paper reports that BCL11A knockdown robustly induces γ-globin in primary adult erythroid progenitors. The same section describes BCL11A as a transcriptional regulator that functions to silence HbF. (LLM, conf=0.94)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Elevated levels of fetal hemoglobin (consisting of two alpha and two gamma chains) are associated with improved morbidity and mortality in patients with TDT and SCD.[20][21][22]”
What the sources say
- Partly supportedcites [20] 20. Musallam KM, Sankaran VG, Cappel- lini MD, Duca L, Nathan DG, Taher AT. Fetal hemoglobin levels and morbidity in untransfused patients with β-thalassemia intermedia. Blood 2012; 119: 364-7. sourceExperimental — accuracy not yet measured
The Introduction reports that HbF modifies morbidity and mortality in adults with sickle cell disease. The Abstract and Results and discussion find lower morbidity with higher HbF in untransfused patients with β-thalassemia intermedia, not transfusion-dependent thalassemia (TDT); the study does not establish a mortality association in TDT. Passage-level page numbers are unavailable in our copy. (LLM, conf=0.88)
- Partly supportedcites [21] 21. Platt OS, Brambilla DJ, Rosse WF, et al. Mortality in sickle cell disease: life expec- tancy and risk factors for early death. N Engl J Med 1994; 330: 1639-44. sourceExperimental — accuracy not yet measured
The Risk Factors for Early Death section (p. 4) links higher fetal hemoglobin to lower mortality in patients with sickle cell anemia, and the Discussion (p. 6) reports improved life expectancy. The paper does not establish that association for transfusion-dependent thalassemia (TDT), or link fetal hemoglobin levels to improved morbidity. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [22] 22. Powars DR, Weiss JN, Chan LS, Schroeder WA. Is there a threshold level of fetal hemoglobin that ameliorates mor- bidity in sickle cell anemia? Blood 1984; 63: 921-6. source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“As a product that is enriched with CD34+ cells, CTX001 may have contributed to the delay in lymphocyte recovery, similar to what has been observed after T-cell-depleted transplantation.33,34”
What the sources say
- Supportedcites [33] 33. Bomberger C, Singh-Jairam M, Rodey G, et al. Lymphoid reconstitution after autologous PBSC transplantation with FACS-sorted CD34+ hematopoietic pro- genitors. Blood 1998; 91: 2588-600. source
The paper’s Discussion (page unavailable) reports delayed quantitative lymphocyte recovery after transplantation with FACS-sorted CD34+ cells compared with conventional PBSC autografts. It also says sorting substantially depleted T cells, supporting the citing sentence’s qualified analogy to T-cell-depleted transplantation. The paper does not study CTX001, and the citing sentence does not claim that it does. (LLM, conf=0.92)
- Not checked — no full text of the sourcecites [34] 34. Nachbaur D, Kropshofer G, Heitger A, et al. Phenotypic and functional lympho- cyte recovery after CD34+-enriched versus non-T cell-depleted autologous peripheral blood stem cell transplantation. J Hema- tother Stem Cell Res 2000; 9: 727-36. source
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Levels of fetal hemoglobin increased rapidly from 0.3 g per deciliter at baseline to 8.4 g per deciliter at month 3, 12.4 g per deciliter at month 12, and 13.1 g per deciliter at month 18 (Fig. 2A).”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“After the administration of CTX001, high levels of edited alleles in bone marrow CD34+ cells and nucleated peripheral-blood cells were maintained (Table 1).”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“After the administration of CTX001 and over time, high levels of edited alleles in bone marrow CD34+ cells and nucleated peripheral-blood cells were maintained (Table 1).”
Strength:plain· not yet calibratedSingle caseTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
- Probably not a substantial claim. 8
- It may state two separate claims as one. 18
- The quote only partly states this claim. 2
Every source the paper cites for this claim was checked and supports it.
In the paper
“The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 nuclease system, a bacterial immune system that can cleave bacteriophage or plasmid DNA, enables programmable targeting of insertions or deletions (indels) at a specific genomic DNA site.28,29”
What the sources say
- Supportedcites [28] 28. Bak RO, Dever DP, Porteus MH. CRISPR/Cas9 genome editing in human hematopoietic stem cells. Nat Protoc 2018; 13: 358-76. sourceExperimental — accuracy not yet measured
The Introduction explains that an sgRNA guides Cas9 to a chosen DNA sequence, where a locus-specific break can be made. It also explains that repair of such breaks can produce insertions or deletions at the break site. Together, these passages support programmable targeting of indels, though indels are a possible repair outcome rather than a guaranteed one. (LLM, conf=0.92)
- Supportedcites [29] 29. Hendel A, Bak RO, Clark JT, et al. Chemically modified guide RNAs enhance CRISPR-Cas genome editing in human pri- mary cells. Nat Biotechnol 2015; 33: 985-9. sourceExperimental — accuracy not yet measured
The paper’s introductory passage (indexed as Abstract; page unavailable) explains that guide RNA directs Cas9 to a chosen genomic DNA sequence and that repair of the resulting break can create insertions or deletions at that site. Its reported experiments also measure targeted indels at specific loci. (LLM, conf=0.93)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Betibeglogene autotemcel, a lentiviral vector-based gene-addition product, is approved in the European Union for the treatment of patients with TDT who have non-β 0 mutations and who do not have a matched sibling donor 14 and is being studied in patients with β 0 /β 0 TDT genotypes and in those with SCD.15,16”
What the sources say
- Not matchedcites [14] 14. European Medicines Agency. Zynteglo: summary of product characteristics (https:// www . ema . europa . eu/ en/ documents/ product -information/ zynteglo -epar -product -information_en . pdf).
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Supportedcites [15] 15. Thompson AA, Walters MC, Kwiat- kowski J, et al. Gene therapy in patients with transfusion-dependent β-thalassemia. N Engl J Med 2018; 378: 1479-93. source
The β0/β0 TDT study clause is supported: the Methods describe two phase 1–2 studies of LentiGlobin BB305, and the patient-characteristics table includes participants with β0/β0 genotypes. The separate EU-approval clause is attached to citation 14, not to the citation for this study. (LLM, conf=0.91)
- Partly supportedcites [16] 16. Ribeil JA, Hacein-Bey-Abina S, Payen E, et al. Gene therapy in a patient with sickle cell disease. N Engl J Med 2017; 376: 848-55. sourceExperimental — accuracy not yet measured
The Discussion reports ongoing studies of the BB305 vector in patients with sickle cell disease and β-thalassemia. It also identifies four recipients as having transfusion-dependent β-thalassemia, but does not specify a β0/β0 genotype. The EU approval statement is attached to a different citation in the citing sentence and is not judged here. (LLM, conf=0.88)
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Not matched
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“an erythroid-specific knockdown of BCL11A delivered by a lentiviral-encoded, microRNA-adapted short hairpin RNA molecule has been shown to reactivate the γ-globin gene and is in early clinical development.[17][18][19]”
What the sources say
- Partly supportedcites [17] 17. Brendel C, Guda S, Renella R, et al. Lineage-specific BCL11A knockdown cir- cumvents toxicities and reverses sickle phenotype. J Clin Invest 2016; 126: 3868- 78. sourceExperimental — accuracy not yet measured
The Results (pp. 4, 6) describe a lentiviral, erythroid-specific BCL11A shRNA-miR vector that induces γ-globin. But the paper calls its findings preclinical (Discussion, p. 8) and says they form the basis for a clinical trial application (p. 1); it does not establish that this approach was already in clinical development. (LLM, conf=0.85)
- Supportedcites [18] 18. Brendel C, Negre O, Rothe M, et al. Preclinical evaluation of a novel lentiviral vector driving lineage-specific BCL11A knockdown for sickle cell gene therapy. Mol Ther Methods Clin Dev 2020; 17: 589- 600. source
The Discussion states that erythroid-specific BCL11A knockdown using a lentiviral shRNAmiR reactivates γ-globin. It also identifies an ongoing pilot and feasibility clinical trial using this approach (NCT03282656). (LLM, conf=0.94)
- Supportedcites [19] 19. Esrick EB, Lehmann LE, Biffi A, et al. Post-transcriptional genetic silencing of BCL11A to treat sickle cell disease. N Engl J Med 2021;384:205-15. source
The Methods describe an open-label pilot study using a lentiviral vector encoding a microRNA-embedded shRNA for erythroid-specific BCL11A knockdown. The Discussion says this approach allows transcription of the endogenous γ-globin gene, supporting both the reactivation and early clinical-development parts of the claim. (LLM, conf=0.94)
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Recently approved therapies, including luspatercept 9 and crizanlizumab, 10 have reduced transfusion requirements in patients with TDT and the incidence of vaso-occlusive episodes in those with SCD, respectively, but neither treatment addresses the underlying cause of the disease nor fully ameliorates disease manifestations.”
What the sources say
- Not checked — no full text of the sourcecites [9] 9. Cappellini MD, Viprakasit V, Taher AT, et al. A phase 3 trial of luspatercept in patients with transfusion-dependent β-thalassemia. N Engl J Med 2020; 382: 1219-31. source
- Supportedcites [10] 10. Ataga KI, Kutlar A, Kanter J, et al. Crizanlizumab for the prevention of pain crises in sickle cell disease. N Engl J Med 2017; 376: 429-39. source
For crizanlizumab, the Discussion reports a 45.3% lower annual pain-crisis rate than placebo, not elimination of crises. It also reports no significant change in markers of hemolysis, while the paper describes crizanlizumab as a P-selectin inhibitor. Together, these passages support that it does not address the underlying cause or fully ameliorate sickle cell disease; this citation does not establish the claim about luspatercept. (LLM, conf=0.87)
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Neonates and infants with TDT or SCD are typically asymptomatic while their fetal hemoglobin levels remain high and become symptomatic during the first year of life when the synthesis of fetal hemoglobin declines 23,24 (Fig. 1A).”
What the sources say
- Partly supportedcites [23] 23. Sankaran VG, Orkin SH. The switch from fetal to adult hemoglobin. Cold Spring Harb Perspect Med 2013; 3(1): a011643. sourceExperimental — accuracy not yet measured
In “THE FETAL-TO-ADULT GLOBIN SWITCH” (page not provided), the paper says infants with β-thalassemia begin to show symptoms as HbF declines in the months after birth. It also links elevated HbF to an asymptomatic period in SCD, but says symptoms appear after infancy rather than during the first year; it discusses β-thalassemia generally, not TDT specifically. (LLM, conf=0.86)
- Partly supportedcites [24] 24. Canver MC, Orkin SH. Customizing the genome as therapy for the β-hemo- globinopathies. Blood 2016; 127: 2536- 45. sourceExperimental — accuracy not yet measured
The Introduction (page not provided) says fetal hemoglobin is silenced in the months after birth and protects against disease severity in β-globin disorders, including SCD and β-thalassemia. It does not say that infants with TDT or SCD are typically asymptomatic while HbF is high or that they become symptomatic during the first year as it falls. (LLM, conf=0.85)
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“the SNPs that are associated with fetal hemoglobin are in an erythroid-specific enhancer, downregulate BCL11A expression, and increase the expression of fetal hemoglobin.1,23”
What the sources say
- Supportedcites [1] 1. Bauer DE, Orkin SH. Hemoglobin switching's surprise: the versatile tran- scription factor BCL11A is a master re- pressor of fetal hemoglobin. Curr Opin Genet Dev 2015; 33: 62-70. source
In “Effects of common genetic variation on BCL11A,” the review places HbF-associated variants in an erythroid enhancer and reports that rs1427407 is associated with reduced BCL11A expression in human erythroid precursors. “Genetic evidence connecting BCL11A and HbF regulation” describes BCL11A as an HbF repressor and reports that reducing it permits HbF expression. Together, these passages support the claimed direction of effect. (LLM, conf=0.90)
- Partly supportedcites [23] 23. Sankaran VG, Orkin SH. The switch from fetal to adult hemoglobin. Cold Spring Harb Perspect Med 2013; 3(1): a011643. sourceExperimental — accuracy not yet measured
The section on early molecular studies reports that variants within BCL11A are associated with HbF levels and that experimentally knocking down BCL11A induces γ-globin expression. It does not say those SNPs lie in an erythroid-specific enhancer or establish that the SNPs themselves lower BCL11A expression and thereby raise HbF. (LLM, conf=0.87)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“During the 21.5 months after receiving CTX001, Patient 1 had 32 adverse events, most of which were considered to be grade 1 or 2 in severity (Table S6).Study investigators classified 2 adverse events as serious: pneumonia in the presence of neutropenia and veno-occlusive liver disease with sinusoidal obstruction syndrome (VOD-SOS), both of which began on study day 13.”
Strength:plain· not yet calibratedSingle caseTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one. The quote only partly states this claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The patient received her last transfusion of packed red cells 30 days after the CTX001 infusion (Fig. 2C).”
Strength:plain· not yet calibratedSingle caseTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“F-cell expression increased from 10.1% at baseline to 99.7% at month 6 and was maintained through month 18 (Fig. 2B).”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Patient 1 was a 19-year-old female with the β 0 /β + (IVS-I-110) genotype of TDT.Before enrollment, she had received 34 units of packed red cells per year, annualized over a 2-year period.”
Strength:plain· not yet calibratedSingle caseTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In immunocompromised mice, there was equivalent engraftment for control and single-guide RNA-edited cells, and the persistence and pattern of edits were stable at 16 weeks, with maintenance of the diversity of edits (Tables S2 and S3 and Fig. S1 in the Supplementary Appendix).”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Patient 2 was a 33-year-old female with SCD (βS/ βS and a single α-globin deletion).In the 2 years before enrollment, she had averaged seven severe vaso-occlusive episodes per year.”
Strength:plain· not yet calibratedSingle caseTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At baseline, the fetal hemoglobin level was 9.1% and the sickle hemoglobin level was 74.1%.At month 3, the fetal hemoglobin level rose to 37.2% and the sickle hemoglobin level was 32.6%.At month 15, the fetal hemoglobin level rose to 43.2% and the sickle hemoglobin increased to 52.3% (Fig. 2D).”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“High frequencies of allelic editing (mean [±SD], 80±6%) were observed and maintained across all subpopulations of CD34+ cells, including long-term hematopoietic stem cells.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The CTX001 drug product had an allelic editing frequency of 68.9%.”
Strength:plain· not yet calibratedSingle caseTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesThe quote only partly states this claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Four other enrolled patients with SCD withdrew from the study before being treated with CTX001 (Table S16).”
Strength:plain· not yet calibratedn = 4Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Patient 2 had 114 adverse events during the 16.6 months after receipt of the CTX001 infusion (Table S11).Study investigators classified 3 adverse events as serious: sepsis in the presence of neutropenia (on day 16), cholelithiasis (on day 49), and abdominal pain (on day 56).All 3 adverse events resolved with treatment.”
Strength:plain· not yet calibratedSingle caseTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Patient 2 had no vaso-occlusive episodes during the 16.6 months after the infusion of CTX001, and the last transfusion of packed red cells was 19 days after infusion (Fig. 2F).”
Strength:plain· not yet calibratedSingle caseTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Without CTX001, the patients' pre-enrollment disease severity would have continued, making pre-enrollment rates a valid comparator.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“F-cell expression was 99.9% at month 5 and was maintained at nearly 100% through month 15, her most recent study visit (Fig. 2E).”
Strength:plain· not yet calibratedSingle caseTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Study investigators observed intermittent, nonserious lymphopenia, which they considered to be probably due to a delay in T-cell recovery after the infusion of CTX001 and which had resolved by study day 351.”
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“An additional limitation of our study is that although we performed comprehensive preclinical on-target and off-target analyses and assays of erythrocyte differentiation, we have not performed similar analyses on clinical samples nor characterized their clonal diversity.”
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The study sponsors (CRISPR Therapeutics and Vertex Pharmaceuticals) designed the study protocols, with oversight provided by the study steering committees and an independent data monitoring committee.”
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Initial results from the follow-up of the first two patients who were treated with CTX001 have shown the intended CRISPR-Cas9 editing of BCL11A in long-term hematopoietic stem cells, with durable engraftment, high levels of fetal hemoglobin expression, and the elimination of vaso-occlusive episodes or need for transfusion.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The clinical improvements after CTX001 are attributable to the gene editing rather than to other aspects of treatment or disease fluctuation.
- Rests on an assumption: Long-term maintenance of edited alleles in peripheral blood reflects editing of long-term hematopoietic stem cells.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The generalizability of these early results with respect to other patients with TDT and SCD remains to be determined.”
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
The paper relies on this without support.
Erythrocytes with high fetal hemoglobin have a survival advantage.
“consistent with an expected survival advantage of erythrocytes with a high level of fetal hemoglobin.”
The paper relies on this without support.
Without CTX001, the patients' pre-enrollment disease severity would have continued, making pre-enrollment rates a valid comparator.
“Before enrollment, she had received 34 units of packed red cells per year, annualized over a 2-year period.”
“In the 2 years before enrollment, she had averaged seven severe vaso-occlusive episodes per year.”
The paper relies on this without support.
The clinical improvements after CTX001 are attributable to the gene editing rather than to other aspects of treatment or disease fluctuation.
“The clinical course of both patients supports our conclusion that CTX001 mimics the phenotype of hereditary persistence of fetal hemoglobin levels.”
The paper relies on this without support.
Long-term maintenance of edited alleles in peripheral blood reflects editing of long-term hematopoietic stem cells.
“Initial results from the follow-up of the first two patients who were treated with CTX001 have shown the intended CRISPR-Cas9 editing of BCL11A in long-term hematopoietic stem cells, with durable engraftment, high levels of fetal hemoglobin expression, and the elimination of vaso-occlusive episodes or need for transfusion.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“CRISPR/Cas-9 for targeted sickle cell disease (SCD) therapy and β-thalassemia have been also applied in clinical trials.23”
From Mechanism and Applications of CRISPR/Cas-9-Mediated Genome Editing (2021) · cites this paper as [23]
Citations
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Base and Prime Editing in the Retina—From Preclinical Research toward Human Clinical Trials
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“CRISPR-Cas9 editing has now been tested in several genetic diseases in various organ systems, ranging from blood diseases [22] to cancer [23].”
BackgroundClinical trials and promising preclinical applications of CRISPR/Cas gene editing
Çerçi, B., Uzay, İ. A., Kara, M. K., & Dinçer, P. (2022) · Life Sciences · doi:10.1016/j.lfs.2022.121204 · Cited by 19
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The challenge of clinical end points in sickle cell disease
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Gene therapy in preeclampsia: the dawn of a new era
Sun, F., de Nieuwburgh, M. P., Hubinont, C., Debiève, F., & Colson, A. (2024) · Hypertension in Pregnancy · doi:10.1080/10641955.2024.2358761 · Cited by 22
“Notably, the first-ever CRISPR-based therapeutic (Casgevy and Lyfgenia) was approved for treating β-thalassemia and sickle cell anemia in the USA and the UK (34,35).”
Katta, V., O’Keefe, K., Li, Y., Mayuranathan, T., Lazzarotto, C. R., Wood, R. K., Levine, R. M., Powers, A., Mayberry, K. D., Manquen, G., et al. (2024) · Molecular Therapy · doi:10.1016/j.ymthe.2024.07.022 · Cited by 20
Self-citationTranscriptional silencing of fetal hemoglobin expression by NonO
Li, X., Chen, M., Liu, B., Lu, P., Lv, X., Zhao, X., Cui, S., Xu, P., Nakamura, Y., Kurita, R., et al. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab671 · Cited by 19
“-globin silencing (17–19).”
Genetic and Epigenetic Therapies for β-Thalassaemia by Altering the Expression of α-Globin Gene
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CRISPR Technology and Its Emerging Applications
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“By disrupting an erythroid enhancer in the BCL11A gene in CD34 þ HSCs, fetal γ -globin (HBG) expression can be reactivated, providing a viable solution for treating SCD and TDT [152].”
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“Preclinical models using CRISPR/Cas9 effectively corrected mutations in metabolic liver diseases like hereditary tyrosinemia type I and sickle cell disease, with clinical trials ongoing for hemoglobinopathies (Frangoul et al., 2021; Esrick et al., 2021).”
Combination of lentiviral and genome editing technologies for the treatment of sickle cell disease
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“Hematologic disorders TDT & SCD BCL11A CRISPR \ Yes No comprehensive genomic analysis of clinical samples and the generalizability of the results needs to be further determined 2021 [71]”
BackgroundHighly specific chimeric DNA-RNA-guided genome editing with enhanced CRISPR-Cas12a system
Kim, H., Lee, W.-J., Kim, C. H., Oh, Y., Gwon, L. W., Lee, H. K., Song, W., Hur, J. K., Lim, K. S., Jeong, K. J., et al. (2022) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2022.03.021 · Cited by 17
Editing human hematopoietic stem cells: advances and challenges
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Self-citationCRISPR/Cas9, a promising approach for the treatment of β-thalassemia: a systematic review
Khiabani, A., Kohansal, M. H., Keshavarzi, A., Shahraki, H., Kooshesh, M., Karimzade, M., & Navashenaq, J. G. (2022) · Molecular Genetics and Genomics · doi:10.1007/s00438-022-01978-z · Cited by 18
“Four out of 21 studies found that mutations in the BCL11A gene promoter suppressed its expression and increased γ-globin expression (Khosravi et al. 2019; Fu et al. 2022; Frangoul et al. 2021; Maroofi et al. 2017).”
BackgroundAdvances in CRISPR/Cas gene therapy for inborn errors of immunity
Liu, X., Li, G., Liu, Y., Zhou, F., Huang, X., & Li, K. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1111777 · Cited by 21
Venkatesan, V., Christopher, A. C., Rhiel, M., Azhagiri, M. K. K., Babu, P., Walavalkar, K., Saravanan, B., Andrieux, G., Rangaraj, S., Srinivasan, S., et al. (2023) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2023.04.024 · Cited by 18
“Two recent 72 clinical studies involving shRNA mediated erythroid specific downregulation of BCL11A and gene 73 editing-mediated disruption of its erythroid-specific enhancer have demonstrated reactivated HbF 74 levels sufficient to reach transfusion independence(10, 11).”
BackgroundMethodKuppers, D. A., Linton, J., Ortiz‐Espinosa, S., McKenna, K. M., Rongvaux, A., & Paddison, P. J. (2023) · PLoS ONE · doi:10.1371/journal.pone.0287052 · Cited by 15
Inborn errors of immunity: A field without frontiers
Bucciol, G., Delafontaine, S., Meyts, I., & Poli, M. C. (2023) · Immunological Reviews · doi:10.1111/imr.13297 · Cited by 21
Corbacioglu, S., Frangoul, H., Locatelli, F., Hobbs, W., & Walters, M. C. (2023) · American Journal of Hematology · doi:10.1002/ajh.27166 · Cited by 19
“All patients engrafted neutrophils and platelets, and the safety profile was consistent with myeloablative busulfan conditioning and autologous HSCT. 50,51 Exa-cel was approved by the Medicines and Healthcare products regulatory Agency in November 2023 for the treatment of both adult and pediatric (12 through 17 years…”
BackgroundInfluentialSelf-citationThe genetic dissection of fetal haemoglobin persistence in sickle cell disease in Nigeria
Ojewunmi, O. O., Adeyemo, T. A., Oyetunji, A. I., Inyang, B. A., Akinrindoye, A., Mkumbe, B. S., Gardner, K., Rooks, H., Brewin, J. N., Patel, H., et al. (2024) · Human Molecular Genetics · doi:10.1093/hmg/ddae014 · Cited by 19
Gupta, A. O., Azul, M., Bhoopalan, S. V., Abraham, A., Bertaina, A., Bidgoli, A., Bonfim, C., Dezern, A. E., Li, J., Louis, C. U., et al. (2024) · Cytotherapy · doi:10.1016/j.jcyt.2024.06.002 · Cited by 17
Self-citationIn vivo evaluation of guide-free Cas9-induced safety risks in a pig model
Ge, W., Gou, S., Zhao, X., Jin, Q., Zhuang, Z., Zhao, Y., Liang, Y., Ouyang, Z., Liu, X., Chen, F., et al. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01905-1 · Cited by 17
“…CRISPR/Cas9-mediated gene therapy has been applied in clinical trials for treating various genetic diseases or refractory conditions, 6 such as sickle cell disease, 7 β -thalassemia, 7,8 transthyretin amyloidosis, 9 retinal degeneration, 10 acquired immunode fi ciency syndrome, 11 and cancers.”
MethodProtective alleles and precision healthcare in crewed spaceflight
Rutter, L. A., MacKay, M. J., Cope, H., Szewczyk, N. J., Kim, J., Overbey, E. G., Tierney, B. T., Muratani, M., Lamm, B., Bezdan, D., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-49423-6 · Cited by 18
Diamantidis, M. D., Ikonomou, G., Argyrakouli, I., Pantelidou, D., & Delicou, S. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252211886 · Cited by 21
“This method can also be applied in SCD [173,176,181].”
Engineered PsCas9 enables therapeutic genome editing in mouse liver with lipid nanoparticles
Degtev, D., Bravo, J. P. K., Emmanouilidi, A., Zdravković, A., Choong, O. K., Touza, J. L., Selfjord, N., Weisheit, I., Francescatto, M., Akçakaya, P., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-53418-8 · Cited by 19
Janoudi, T., Jagdale, M., Wu, M., Gorlla, S., Zhang, P., Shao, Y., Li, L., Bowley, S. R., Marco, E., & Chang, K.-H. (2024) · Blood Advances · doi:10.1182/bloodadvances.2024014040 · Cited by 17
An evolving understanding of multiple causal variants underlying genetic association signals
Long, E., Williams, J., Zhang, H., & Choi, J. (2025) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2025.01.018 · Cited by 18
Effect of SARS-CoV-2 Infection on Pregnancy Outcomes in an Inner-City Black Patient Population
Liu, C., Andrusier, M. A., Silver, M. P., Applewhite, L., & Clare, C. A. (2021) · Journal of Community Health · doi:10.1007/s10900-021-00988-z · Cited by 17
Novel therapies in β‐thalassaemia
Grech, L., Borg, K., & Borg, J. (2021) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.14918 · Cited by 18
Shy, B. R., Vykunta, V. S., Ha, A. S., Roth, T. L., Talbot, A., Nguyen, D. N., Chen, Y. Y., Blaeschke, F., Vedova, S., Mamedov, M. R., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.09.02.458799 · Cited by 18
Self-citationDrahos, J., Boateng-Kuffour, A., Calvert, M., et al. (2024) · Patient · doi:10.1007/s40271-024-00678-7 · Cited by 17
“…associated with conventional treatments; several novel gene therapies that aim to provide curative options for individuals with TDT, therapies that can eliminate the need for and consequences associated with lifelong RBCTs and ICT are currently being evaluated in clinical trials [15, 27, 28].”
BackgroundAnemia and iron overload as prognostic markers of outcomes in β-thalassemia
Musallam, K. M., Sheth, S., Cappellini, M. D., Forni, G. L., Maggio, A., & Taher, A. T. (2024) · Expert Review of Hematology · doi:10.1080/17474086.2024.2383420 · Cited by 18
Self-citationMolaei, Z., Jabbarpour, Z., Omidkhoda, A., & Ahmadbeigi, N. (2024) · Stem Cell Research & Therapy · doi:10.1186/s13287-024-03848-4 · Cited by 17
“…disease (AD) [19], AIDS [20], autoimmune diseases [21], cystic fibrosis [22, 23], Huntington’s chorea disorder [24], Duchenne muscular dystrophy [25], chronic granulomatous disease [26], retinitis pigmentosa [27], hemophilia [28, 29], sickle cell disease (SCD) [30–32] and thalas-semia [31, 33, 34].”
BackgroundRuminski, P., Rettig, M. P., & DiPersio, J. F. (2024) · Biomolecules · doi:10.3390/biom14081003 · Cited by 16
“Hematopoietic stem and progenitor cells (HSPCs) are required for both autologous and allogeneic hematopoietic stem cell transplantation (HSCT) and, more recently, HSPC-based gene therapies being developed to treat genetic diseases such as sickle-cell anemia [1,2].”
BackgroundIn vivo liver targeted genome editing as therapeutic approach: progresses and challenges
Simoni, C., Barbon, E., Muro, A. F., & Cantore, A. (2024) · Frontiers in Genome Editing · doi:10.3389/fgeed.2024.1458037 · Cited by 20
“As a result of the BCL11A inactivation, the reactivation of fetal hemoglobin allows for restoring erythropoietic homeostasis (Frangoul et al., 2021).”
Exploring the therapeutic potential of modulating nonsense-mediated mRNA decay
McMahon, M., & Maquat, L. E. (2024) · RNA · doi:10.1261/rna.080334.124 · Cited by 16
“…of genome engineering by CRISPR – Cas9 (Doudna and Charpentier 2014), CRISPR – Cas9-me-diated gene editing has become an invaluable tool for bio-medical research and an approved treatment option for some diseases, including the use of Casgevy for sickle cell disease (Frangoul et al. 2021).”
Far, B. F., Akbari, M., Habibi, M. A., Katavand, M., & Nasseri, S. (2025) · Cell Proliferation · doi:10.1111/cpr.70099 · Cited by 23
Botchkarev, V. V., Harrington, S., Stoppato, M., Justen, A., Kimber, C., Kapuria, A., Gibson, K. M., Chu, C.-S., Xu, Y., Haugh, K. A., et al. (2025) · Nature Biotechnology · doi:10.1038/s41587-025-02915-2 · Cited by 22
Gene Editing for Inherited Red Blood Cell Diseases
Bustamante, O. Q., Fañanas-Baquero, S., Dessy-Rodríguez, M., Ojeda-Pérez, I., & Segovia, J. C. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.848261 · Cited by 20
Targeting fetal hemoglobin expression to treat β hemoglobinopathies
Steinberg, M. H. (2022) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2022.2066519 · Cited by 16
“There were no off-target effects of gene editing [27].”
BackgroundSelf-citationTherapeutic approaches to activate the canonical Wnt pathway for bone regeneration
Nelson, A. L., Fontana, G., Miclau, E., Rongstad, M., Murphy, W. L., Huard, J., Ehrhart, N. P., & Bahney, C. S. (2022) · Journal of Tissue Engineering and Regenerative Medicine · doi:10.1002/term.3349 · Cited by 15
Global perspectives on cellular therapy for children with sickle cell disease
John, T. D., Namazzi, R., Chirande, L., & Tubman, V. N. (2022) · Current Opinion in Hematology · doi:10.1097/moh.0000000000000738 · Cited by 17
“The success of first-in-human feasibility, safety, and efficacy trials have naturally prompted consideration of global applicability [57,58].”
BackgroundDeng, J., & McReynolds, L. J. (2022) · Current Opinion in Pediatrics · doi:10.1097/mop.0000000000001196 · Cited by 16
CRISPR medicine for blood disorders: Progress and challenges in delivery
Gol, T. M., Ureña-Bailén, G., Hou, Y., Sinn, R., Antony, J. S., Handgretinger, R., & Mezger, M. (2023) · Frontiers in Genome Editing · doi:10.3389/fgeed.2022.1037290 · Cited by 16
“In these clinical trials, hematopoietic stem cells are electroporated with CRISPR-Cas9 to target the BCL11A gene and demonstrated to produce high levels of fetal hemoglobin (Frangoul et al., 2021).”
BackgroundSelf-citationCorrecting inborn errors of immunity: From viral mediated gene addition to gene editing
Castiello, M. C., Ferrari, S., & VILLA, A. M. (2023) · Seminars in Immunology · doi:10.1016/j.smim.2023.101731 · Cited by 16
Alayoubi, A. M., Khawaji, Z. Y., Mohammed, M. A., & Mercier, F. (2023) · Annals of Hematology · doi:10.1007/s00277-023-05457-2 · Cited by 24
“…were related to the studies but not the gene editing have occurred and resolved thereafter, including pneumonia in the presence of neutropenia, sepsis in the presence of neutropenia, thrombocytopenia, cholelithiasis, and veno-occlusive liver disease with sinusoidal obstruction syndrome [53–55].”
Natural Biopolymer-Based Delivery of CRISPR/Cas9 for Cancer Treatment
Lin, M., & Wang, X. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics16010062 · Cited by 18
“Over ten clinical trials are now currently underway [3,14], including CRISPR/Cas9-based therapy for acute lymphoblastic leukemia [15], transthyretin amyloidosis [16], sickle cell disease, and β -thalassemia [17,18], and the initial results have been promising [14].”
BackgroundGenome editing and its role in vaccine, diagnosis, and therapeutic advancement
Bisht, D., Salave, S., Desai, N., Gogoi, P., Rana, D., Biswal, P., Sarma, G., Benival, D. M., Kommineni, N., & Desai, D. N. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.131802 · Cited by 16
Functional overlap between the mammalian Sar1a and Sar1b paralogs in vivo
Tang, V. T., Xiang, J., Chen, Z., McCormick, J., Abbineni, P. S., Chen, X., Hoenerhoff, M. J., Emmer, B. T., Khoriaty, R. N., Lin, J. D., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2322164121 · Cited by 17
How I manage iron overload in the hematopoietic cell transplantation setting
Angelucci, E. (2024) · Blood · doi:10.1182/blood.2023022500 · Cited by 16
CRISPR/Cas9 screening: unraveling cancer immunotherapy’s ‘Rosetta Stone’
Chen, B., Deng, Y., Ren, X., Zhao, J., & Jiang, C. (2024) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2024.04.014 · Cited by 17
Banda, A., Impomeni, O., Singh, A., Baloch, A. R., Hu, W., & Jaijyan, D. K. (2024) · Vaccines · doi:10.3390/vaccines12060636 · Cited by 16
“Researchers have utilized CRISPR-Cas to pinpoint the BCL11A gene in stem cell patients with beta-thalassemia [222].”
BackgroundMethodInfluentialKansal, R. (2024) · Genes · doi:10.3390/genes15070863 · Cited by 21
“The base editors described above had entered the clinic by 2022, including in sickle cell disease [101,102].”
BackgroundGene therapy for ultrarare diseases: a geneticist’s perspective
Hwu, W. (2024) · Journal of Biomedical Science · doi:10.1186/s12929-024-01070-1 · Cited by 16
Next-generation CRISPR technology for genome, epigenome and mitochondrial editing
Lau, C., Liang, Q., & Zhu, H. (2024) · Transgenic Research · doi:10.1007/s11248-024-00404-x · Cited by 19
Recent advancements in gene therapy for sickle cell disease and β-thalassemia
Li, L., & Mandal, P. K. (2024) · Frontiers in Hematology · doi:10.3389/frhem.2024.1468952 · Cited by 23
NANOSPRESSO: toward personalized, locally produced nucleic acid nanomedicines
Sentí, M. E., Ceccaldi, A., Luciani, M., Saber, N., Schürmann, P. J. L., Geerlings, M. W., Hölig, P., de Beer, J., Hannus, M., Campbell, F., et al. (2025) · Frontiers in Science · doi:10.3389/fsci.2025.1458636 · Cited by 17
Molecular analysis of the erythroid phenotype of a patient with BCL11A haploinsufficiency
Wessels, M. W., Cnossen, M. H., van Dijk, T. B., Gillemans, N., Schmidt, K. L. J., van Lom, K., Vinjamur, D. S., Coyne, S. M., Kurita, R., Nakamura, Y., et al. (2021) · Blood Advances · doi:10.1182/bloodadvances.2020003753 · Cited by 16
Delta‐globin gene expression improves sickle cell disease in a humanised mouse model
Porcu, S., Simbula, M., Marongiu, M. F., Perra, A., Poddie, D., Perseu, L., Kowalik, M. A., Littera, R., Barella, S., Caria, C. A., et al. (2021) · British Journal of Haematology · doi:10.1111/bjh.17561 · Cited by 19
The Role of miRNAs as Therapeutic Tools in Sickle Cell Disease
Cyrus, C. (2021) · Medicina · doi:10.3390/medicina57101106 · Cited by 18
“, [9] recapitulated the hereditary persistence of fetal hemoglobin phenotype by suppressing BCL11A expression using CRISPR-Cas9 gene-editing techniques in CD34+ hematopoietic stem and progenitor cells at the erythroid-specific enhancer region.”
BackgroundMethodPrimary HBB gene mutation severity and long‐term outcomes in a global cohort of β‐thalassaemia
Musallam, K. M., Vitrano, A., Meloni, A., Pollina, S. A., Marco, V. D., Ansari, S. H., Filosa, A., Ricchi, P., Ceci, A., Daar, S., et al. (2021) · British Journal of Haematology · doi:10.1111/bjh.17897 · Cited by 16
Poletto, É., Colella, P., Vera, L. N. P., Khan, S. A., Tomatsu, S., Baldo, G., & Gomez‐Ospina, N. (2022) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2022.04.009 · Cited by 18
Recent advances in “sickle and niche” research - Tribute to Dr. Paul S Frenette -
Torres, L. S., Asada, N., Weiss, M. J., Trumpp, A., Suda, T., Scadden, D. T., & Ito, K. (2022) · Stem Cell Reports · doi:10.1016/j.stemcr.2022.06.004 · Cited by 19
“A patient infused with autologous CRISPRCas9-edited HSCs (genetically modified to restore the production of HbF), showed high levels of HbF, resolution of vaso-occlusive episodes, and transfusion independence (Frangoul et al., 2021).”
BackgroundCRISPR/Cas: History and Perspectives
Shmakova, A., Shmakova, O. P., Karpukhina, A. A., & Vassetzky, Y. S. (2022) · Russian Journal of Developmental Biology · doi:10.1134/s1062360422040075 · Cited by 17
“Группа доктора Хайдара Франгула (Haydar Frangoul) осуществила редактирование гематопоэтических стволовых клеток с целью нокаута энхансера BCL11A у двух пациентов с серповидно-клеточной анемией и β -талассемией (моногенные заболевания, вы-званные мутациями гена HBB, кодирующего β -субъединицу…”
BackgroundInfluentialClaiborne, D. T., Detwiler, Z., Docken, S. S., Borland, T. D., Cromer, D., Simkhovich, A., Ophinni, Y., Okawa, K., Bateson, T., Chen, T., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-55873-3 · Cited by 16
Self-citationErythropoiesis: insights from a genomic perspective
Ji, H. Y. (2024) · Experimental & Molecular Medicine · doi:10.1038/s12276-024-01311-1 · Cited by 22
Walters, M. C., Eapen, M., Liu, Y., Rassi, F. A. E., Waller, E. K., Levine, J. E., Strouse, J. J., Antin, J. H., Parikh, S. H., Bakshi, N., et al. (2024) · Blood Advances · doi:10.1182/bloodadvances.2024013926 · Cited by 18
“20-22 We attempted to characterize differences between the donor and no donor arms, but limited participation throughout the 2-year period after biologic assignment limited an opportunity for ef fi cient comparison between the treatment arms.”
Cardiac injury caused by iron overload in thalassemia
Fu, C., & Yang, X. Y. (2025) · Frontiers in Pediatrics · doi:10.3389/fped.2025.1514722 · Cited by 16
Therapeutic in vivo genome editing: innovations and challenges in rAAV vector-based CRISPR delivery
Gil, J.-S., Lee, S., & Koo, T. (2025) · Gene Therapy · doi:10.1038/s41434-025-00573-2 · Cited by 19
Hoffmann, D., Sens, J., Brennig, S., Brand, D., Philipp, F., Barbosa, P. V., Kuehle, J., Steinemann, D., Lenz, D., Buchegger, T., et al. (2021) · Journal of Personalized Medicine · doi:10.3390/jpm11030221 · Cited by 17
“In recent years, CRISPR-Cas9 opened new avenues for genome editing for basic research and clinical applications [31,32].”
BackgroundIn vivo targeting of a variant causing vanishing white matter using CRISPR/Cas9
Hillen, A. E. J., Hruzova, M., Rothgangl, T., Breur, M., Bugiani, M., van der Knaap, M. S., Schwank, G., & Heine, V. M. (2022) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2022.02.006 · Cited by 17
Gantz, V. M., & Bier, E. (2022) · BioEssays · doi:10.1002/bies.202100279 · Cited by 14
A Curative DNA Code for Hematopoietic Defects
Porteus, M. H., Pavel-Dinu, M., & Pai, S. (2022) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2022.05.002 · Cited by 15
Emergent treatments for β-thalassemia and orphan drug legislations
Costa, E., Cappellini, M. D., Rivella, S., Chilin, A., Alessi, E., Riccaboni, M., Leufkens, H. G. M., & Luzzatto, L. (2022) · Drug Discovery Today · doi:10.1016/j.drudis.2022.103342 · Cited by 14
Self-citationIn vivo application of base and prime editing to treat inherited retinal diseases
Jo, D. H., Bae, S., Kim, S., Kim, J., & Kim, J. H. (2022) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2022.101132 · Cited by 15
Huang, C., Li, Q., & Li, J. (2022) · Medical Review · doi:10.1515/mr-2022-0029 · Cited by 20
Delivery challenges for CRISPR—Cas9 genome editing for Duchenne muscular dystrophy
Padmaswari, M. H., Agrawal, S., Jia, M. S., Ivy, A., Maxenberger, D. A., Burcham, L. A., & Nelson, C. E. (2023) · Biophysics Reviews · doi:10.1063/5.0131452 · Cited by 18
Gene Therapy for Inborn Errors of Immunity
Arlabosse, T., Booth, C., & Candotti, F. (2023) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2023.04.001 · Cited by 15
Advances and Challenges in the Development of Gene Therapy Medicinal Products for Rare Diseases
Bueren, J. A., & Auricchio, A. (2023) · Human Gene Therapy · doi:10.1089/hum.2023.152 · Cited by 17
The Dawn of In Vivo Gene Editing Era: A Revolution in the Making
Niazi, S. K. (2023) · Biologics · doi:10.3390/biologics3040014 · Cited by 17
Global analysis of suppressor mutations that rescue human genetic defects
Ünlü, B., Pons, C., Ho, U. L., Batté, A., Aloy, P., & van Leeuwen, J. S. (2023) · Genome Medicine · doi:10.1186/s13073-023-01232-0 · Cited by 14
Metadata
- Authors
- Frangoul, H., Altshuler, D., Cappellini, M. D., Chen, Y.-S., Domm, J., Eustace, B. K., Foell, J., de la Fuente, J., Grupp, S., Handgretinger, R., Ho, T. W., Kattamis, A., Kernytsky, A., Lekstrom-Himes, J., Li, A. M., Locatelli, F., Mapara, M. Y., de Montalembert, M., Rondelli, D., Sharma, A., Sheth, S., Soni, S., Steinberg, M. H., Wall, D., Yen, A., & Corbacioglu, S.
- Affiliations
- Boston University (US)
- From the Sarah Cannon Center for Blood Cancer at the Children’s Hospital at TriStar Centennial, Nashville (H.F., J.D.), and St. Jude Children’s Research Hospital, Memphis (A.S.) — both in Tennessee; Vertex Pharmaceuticals (D.A., B.K.E., J.L.-H., A.Y.) and Boston University School of Medicine (M.H.S.), Boston, and CRISPR Therapeutics, Cambridge (Y.-S.C., T.W.H., A. Kernytsky, S. Soni) — both in Massachusetts; the University of Milan, Milan (M.D.C.), and Ospedale Pediatrico Bambino Gesù Rome, Sapienza...
- ORCID
- Frangoul, Haydar
- Altshuler, David
- Cappellini, M. Domenica
- Chen, Yi-Shan
- Grupp, Stephan
- Handgretinger, Rupert
- Ho, Tony W.
- Kattamis, Antonis
- Lekstrom-Himes, Julie
- Li, Amanda M.
- Locatelli, Franco
- Mapara, Markus Y.
- Rondelli, Damiano
- Sharma, Akshay
- Sheth, Sujit
- Soni, Sandeep
- Steinberg, Martin H.
- Wall, Donna
- Corbacioglu, Selim
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2021-01-21
- Volume
- 384
- Issue
- 3
- Pages
- 252-260
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W3112179900
- Semantic Scholar
- 07c69f7ddd34ca8c80618e16981e2fbdb0de6529
- Cited by
- 1,962
- References
- 35
- Citations by year
- 2026: 330 · 2025: 342 · 2024: 392 · 2023: 333 · 2022: 323 · 2021: 232
- FWCI
- 116.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- University of Regensburg Publication Server (University of Regensburg) (submittedVersion)
- Funders
- CRISPR Therapeutics AG
- Vertex Pharmaceuticals Incorporated
- Topics
- Health Sciences › Medicine › Genetics (clinical) › Hemoglobinopathies and Related Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Keywords
- sickle cell disease, beta-thalassemia, CRISPR/Cas9 genome editing, fetal hemoglobin, hematopoietic stem cell transplantation, autologous hematopoietic stem cells, electroporation, transfusion independence, vaso-occlusive crisis
- MeSH terms
- Gene Editing, Adult, Anemia, Sickle Cell, Female, Fetal Hemoglobin, Humans, Repressor Proteins, Genetic Therapy, beta-Thalassemia, Young Adult, CRISPR-Cas Systems
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