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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Self-citationChemically modified guide RNAs enhance CRISPR-Cas genome editing in human primary cells
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BCL11A enhancer dissection by Cas9-mediated in situ saturating mutagenesis
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An Erythroid Enhancer of BCL11A Subject to Genetic Variation Determines Fetal Hemoglobin Level
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Items 1,301–1,400 of 1,950
The Novel Role of the B-Cell Lymphoma/Leukemia 11A (BCL11A) Gene in β-Thalassaemia Treatment
Lai, M. I., & Ahmed, N. H. M. (2022) · Cardiovascular & Haematological Disorders - Drug Targets · doi:10.2174/1871529x23666230123140926 · Cited by 3
Stem Cell-Based Therapeutic Approaches in Genetic Diseases
Aslan, A., & Yuka, S. A. (2023) · Advances in experimental medicine and biology · doi:10.1007/5584_2023_761 · Cited by 2
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How has CRISPR Transformed Therapeutic Drug Discovery?
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Gene correction for sickle cell disease hits its prime
Levesque, S., & Bauer, D. E. (2023) · Nature Biomedical Engineering · doi:10.1038/s41551-023-01040-2 · Cited by 2
One and Done? How CRISPR Is Changing the Clinical Outlook for Multiple Diseases
Cowen, L. (2023) · Inside Precision Medicine · doi:10.1089/ipm.10.03.04 · Cited by 2
Real-life experience with luspatercept in transfusion-dependent β-thalassemia
Roccotelli, D., Grande, D., Cicco, G., Palma, A. M., Longo, M. C., Albano, F., Vitucci, A., & Musto, P. (2023) · Annals of Hematology · doi:10.1007/s00277-023-05381-5 · Cited by 3
“Advancements in β-thalassemia therapy [2, 3] include emerging treatments like gene therapy [4, 5] and erythroid maturation agents [6, 7].”
BackgroundNonchromatographic Purification of Synthetic RNA
McClain, I., Dagci, H., & Royzen, M. (2023) · Springer eBooks · doi:10.1007/978-981-19-9776-1_84 · Cited by 2
Finding Needles in the Haystack: Strategies for Uncovering Noncoding Regulatory Variants
Chen, Y., Paramo, M. I., Zhang, Y., Li, Y., Shah, S. R., Jin, Y., Zhang, J., Pan, X., & Yu, H. (2023) · Annual Review of Genetics · doi:10.1146/annurev-genet-030723-120717 · Cited by 3
Self-citationGenome-Editing – Gentherapie 2.0 oder nur eine Wunschvorstellung?
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Mangla, A., Ehsan, M., Agarwal, N., & Maruvada, S. (2019) · StatPearls · Cited by 2
Assessing Off-Target Editing of CRISPR-Cas9 Systems
Pruett‐Miller, S. M. (2020) · The CRISPR Journal · doi:10.1089/crispr.2020.29116.smi · Cited by 2
Minimal Amelogenin Domain for Enamel Formation
Geng, S., Lei, Y., & Snead, M. L. (2021) · JOM · doi:10.1007/s11837-021-04687-x · Cited by 2
A framework for evaluating edited cell libraries created by massively parallel genome engineeringPreprint
Cawley, S. E., Abbate, E., Abraham, C. G., Alvarez, S., Barber, M., Bolte, S., Bruand, J., Church, D. M., Davis, C., Estes, M., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.09.23.458228 · Cited by 2
In Through the Out Door: Editas' CEOs Grasp Opportunities Amidst Challenges
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Editorial: Ex-vivo and in-vivo genome engineering for metabolic and neurometabolic diseases
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“Therapeutic NHEJ has been successfully applied ex vivo to modify CD34+ hematopoietic stem and progenitor cells (HSPCs) from individuals affected by beta-Thalassemia (b-Thal) and Sickle cell disease (SCD), both caused bymutations in the β-globin gene (HBB) (Ledford, 2020; Frangoul et al., 2021).”
Method[Gene therapy strategies and prospects for neurofibromatosis type 1].
Zheng, T., Zhu, B., Wang, Z., & Li, Q. (2024) · PubMed Central · doi:10.7507/1002-1892.202309071 · Cited by 2
Beyond Genome-Wide Scans: Advancing Hypertension Genomics Into the Future
Padmanabhan, S., Delles, C., & Dominiczak, A. F. (2024) · Hypertension · doi:10.1161/hypertensionaha.124.21371 · Cited by 2
Freimann, K., Brümmer, A., Warmerdam, R., Rupall, T. S., Hernández-Ledesma, A. L., Chiou, J., Holzinger, E. R., Maranville, J., Nakić, N., Ongen, H., et al. (2024) · medRxiv · doi:10.1101/2024.07.15.24310442 · Cited by 2
“In a prominent example, an erythrocyte-specific regulatory element first identified as a trans protein QTL ( trans -pQTL) for foetal haemoglobin (HbF) was used to design the first ever gene editing therapy for sickle-cell disease 2,3 .”
Scalable assessment of genome editing off-targets associated with genetic variantsPreprint
Lin, J., Nguyen, M. A., Lin, L. Y., Zeng, J., Verma, A., Neri, N. R., da Silva, L. F., Mucci, A., Wolfe, S. A., Shaw, K. L., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.07.24.605019 · Cited by 3
“We tested the gRNA sg1617 25 used in exa-cel, the first FDA-approved gene edited cell therapy, which disrupts the BCL11A +58 erythroid enhancer and induces fetal hemoglobin (HbF) for β-hemoglobinopathy patients.”
BackgroundMethodResultInfluentialThe Ethics of Gene Therapy for Sickle Cell Disease
Patel, A., & Kuo, A. A. (2025) · Cureus · doi:10.7759/cureus.81037 · Cited by 2
Liao, J., Zhang, H., Chen, S., Hsiao, S., Lai, C.-P., Hu, F., Ren, W., Feng, C., Xie, D., Zheng, Y., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.05.14.653640 · Cited by 3
First in man: gene editing for the treatment of transthyretin amyloidosis
Liuzzo, G., & Patrono, C. (2021) · European Heart Journal · doi:10.1093/eurheartj/ehab542 · Cited by 1
Does the world need germline editing for β-thalassemia?
Kulozik, A. E. (2021) · Haematologica · doi:10.3324/haematol.2021.279998 · Cited by 1
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Self-citationAvances en terapia génica en humanos: algunos conceptos básicos y un recorrido histórico
Silva, G. E. (2022) · Revista Médica Clínica Las Condes · doi:10.1016/j.rmclc.2022.03.001 · Cited by 4
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Self-citationGenomic editing: From human health to the “perfect child”
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Zebrafish for the Study of Enhancer Activity in Human Traits and Disease
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Charoenkwan, P., Komwilaisak, P., Thepsuthummarat, K., et al. (2024) · Thalassemia Reports · doi:10.3390/thalassrep14010002 · Cited by 1
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“Two patients, one with transfusion-dependent β -thalassemia (TDT) and the other with sickle cell disease (SCD), were effectively cured after receiving treatment for one year [42].”
BackgroundLes complications de la drépanocytose, de l’enfant à l’adulte
de Montalembert, M., Pinhas, Y., Brice, J., & Taylor, M. (2024) · Bulletin de l Académie Nationale de Médecine · doi:10.1016/j.banm.2024.02.016 · Cited by 1
Self-citationCell-based medicinal products: a review of current research
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“Promising results are emerging from ongoing gene therapy trials involving patients with typical β-thalassemia [22,23].”
Transcriptional regulators of fetal hemoglobin
dos Santos, G. P., Rabi, L. T., Bezerra, A. A., da Cunha, M. R., Iatecola, A., & Fernandes, V. A. R. (2024) · Hematology Transfusion and Cell Therapy · doi:10.1016/j.htct.2024.06.001 · Cited by 1
Genetic modifications of EGLN1 reactivate HbF production in β0-thalassemia/HbE
Jan‐ngam, V., Boontha, S., Tubsuwan, A., Wongpalee, S. P., Fanhchaksai, K., Tantiworawit, A., Charoenkwan, P., & Khamphikham, P. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e38020 · Cited by 1
“BCL11A is the well-known γ -globin regulator that has proven as effective therapeutic target for β -thalassemia disease [10 – 13].”
Scaling of cell and gene therapies to population
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The Mortality of Adults With Sickle Cell Disease at a Comprehensive Sickle Cell Center
Afranie‐Sakyi, J. A., Randall, E., Fasano, R. M., McLemore, M. L., & Rassi, F. A. E. (2025) · European Journal Of Haematology · doi:10.1111/ejh.14360 · Cited by 2
Saberi, F., Yousefi-Najafabadi, Z., Shams, F., Dehghan, Z., Ahmadi, S., Pilehchi, T., Noori, E., Esmaeelzadeh, Z., Bazgiri, M., Mohammadi, R., et al. (2025) · Current Gene Therapy · doi:10.2174/0115665232345516241119070150 · Cited by 3
Medicaid and the Promise for Cure
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A quick guide to evaluating prime editing efficiency in mammalian cells
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Une approche CRISPR/Cas pour traiter les β-hémoglobinopathies
Brusson, M., & Miccio, A. (2025) · médecine/sciences · doi:10.1051/medsci/2024191 · Cited by 2
Assessment of Miniature AsCas12f1 Variants for Gene Editing and Activation
Ren, C., & Bao, Z. (2025) · Biotechnology and Bioengineering · doi:10.1002/bit.28978 · Cited by 1
“CRISPR/Cas systems have greatly facilitated the development of novel gene therapies (Frangoul et al. 2021; Zhang et al. 2021).”
Palani, C. D., Smith, A., Cao, X., Li, Y., Pace, B. S., & Starlard‐Davenport, A. (2025) · British Journal of Haematology · doi:10.1111/bjh.20107 · Cited by 1
“26 Despite this positive outcome, concerns regarding potential off-target effects and challenges related to accessibility and cost for gene therapy have surfaced.”
‘Emerging cell-specific therapies in cardiovascular disease’
Mondal, A. R., & Misra, A. (2025) · Vascular Pharmacology · doi:10.1016/j.vph.2025.107516 · Cited by 1
Rangraze, I. R., Khan, S. S., Jhancy, M., et al. (2025) · Journal Of Advanced Pharmacy Education And Research · doi:10.51847/4jxzynaqtb · Cited by 1
Thalassemia syndromes and other hemoglobinopathies
Sheth, S. (2025) · doi:10.1182/ashsap9.chapter10 · Cited by 1
Self-citationEfficient gene disruption with CRISPR–Cas3 in human T cells
Fujii, T., Sakoda, Y., Yoshimi, K., Takeshita, K., Watanabe, S., Iida, R., Obo, T., Yokoyama, K., Tamada, K., & Mashimo, T. (2026) · NAR Cancer · doi:10.1093/narcan/zcag009 · Cited by 1
Alahmari, A. D., Alghamdi, S. A., Alasbali, R., Samarkandi, S. H., Alqahtani, S. A., Samarkandi, H. H., Ahmed, S. O., Broering, D., Alzahrani, H. A., Kassim, A. A., et al. (2025) · Communications Medicine · doi:10.1038/s43856-025-01040-0 · Cited by 2
El-Awaisi, J., Perrella, G., Mayor, N., Tinkova, V. V., Cleary, S. J., Grygielska, B., Watson, S. P., Dimitrov, J. D., Brill, A. G., Hassan, E., et al. (2025) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.124.322072 · Cited by 3
Al, T. M. (2025) · Journal of Hematology and Clinical Research · doi:10.29328/journal.jhcr.1001035 · Cited by 1
Cas9 beyond CRISPR – SUMOylation , effector‐like potential and pathogenic adaptation
Şahin, U. (2025) · FEBS Journal · doi:10.1111/febs.70256 · Cited by 1
TARGETED DRUG DELIVERY THROUGH CRISPR‒CAS9: BRIDGING BIOPHARMACEUTICS AND PHARMACOKINETICS
Ramasamy, J., Jaisankar, D., RAMAMOORTHY, S., Jothibasu, D., & RAVIKUMAR, N. (2025) · International Journal of Applied Pharmaceutics · doi:10.22159/ijap.2025v17i5.54502 · Cited by 1
BCL11A deficiency protects epidermis from UVB-induced damage through promotion of autophagy
Deng, X., Liu, H., Wang, X., Dong, X., Fu, Z.-Z., Niu, X., Guo, Z. R., Lian, P., Deng, Y., Ding, Z., et al. (2025) · Communications Biology · doi:10.1038/s42003-025-08814-1 · Cited by 1
“This well-established fi nding has led to the development of the BCL11A gene-editing therapy, whichtheFDAhasapprovedfortheclinical treatmentofsicklecell anemia and beta thalassemia 10,12 .”
Chatterjee, G., & Singh, K. K. (2025) · Genetics. · doi:10.5772/intechopen.1012378 · Cited by 2
Advances in Hemoglobinopathies: From Molecular Insights to Therapeutic Innovations
Davarnia, B., & Arish, S. (2025) · IntechOpen eBooks · doi:10.5772/intechopen.1009772 · Cited by 1
Yang, M. J., Liu, S., Chen, G., Liu, X., Sun, D., Zhang, J., Wang, Y., Chen, S., Tian, R., & Hu, Z. (2025) · Cell Genomics · doi:10.1016/j.xgen.2025.101039 · Cited by 1
Emerging Therapies for Sickle Cell Disease: From Symptom Management to Curative Gene Therapy
Duesberg, M., & Schiller, G. J. (2025) · Cureus · doi:10.7759/cureus.95112 · Cited by 3
“In the HGB-206 study, 28 of 32 evaluable patients experienced complete resolution of severe VOEs, with sustained HbAT87Q expression and reduced hemolysis markers [44,46-47,57-58”
InfluentialLindquist, M., Stafie, S. T., Ward, C., et al. (2025) · Journal of American Association for Pediatric Ophthalmology and Strabismus · doi:10.1016/j.jaapos.2025.104683 · Cited by 1
Li, G., Zhao, Y., Liu, R., Du, W., & Zhang, Y. (2025) · Stem Cell Reviews and Reports · doi:10.1007/s12015-025-10991-9 · Cited by 1
“Gene editing technology holds irreplaceable therapeutic value and also represents a crucial approach for treating hereditary blood disorders (such as Sickle Cell Disease and β-Thalassemia) [65], inherited immune deficiencies, cancer, and metabolic diseases.”
CRISPR-based gene therapy for huntington’s disease: current advances and future prospects
Zaheer, A., AboQuella, N. M., Wadan, A. S., Saad, H. A., Kumar, D., Panjwani, S., Rath, S., & Ahmed, S. I. (2025) · Neurogenetics · doi:10.1007/s10048-025-00858-z · Cited by 2
“An overall success rate of 60–70% has been noted across all diseases, thus holding great potential for a complete cure [19, 20].”
Sweileh, M. W. (2025) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-025-03957-0 · Cited by 1
Shan, X., Li, Q., Wang, M., Niu, Y., Sun, Z., Ma, X., Wang, T., Tong, X., Zhang, J., & Niu, D. (2025) · Functional & Integrative Genomics · doi:10.1007/s10142-025-01756-1 · Cited by 1
Hara, Y., Lemgart, V. T., Lessard, S., Mercadante, C. J., Ribeil, J., Hicks, A., Rimmelé, P., & Light, D. R. (2025) · Science Advances · doi:10.1126/sciadv.adx1144 · Cited by 1
“There is ongoing interest in innovative cell and gene therapy approaches that either increase HbF expression directly ( 11 – 13 ) or express a modified adult hemoglobin HbA T87Q (T87Q for amino acid substitution threonine to glutamine at position 87) containing Gln 87 ( 14 , 15 ).”
The development of an advanced lentiviral gene therapy for beta-thalassemia
Liu, H., Wang, Y., Zhang, R., & Chang, L. (2025) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2025.152963 · Cited by 1
Jang, Y., Eom, Y. J., Gwak, S.-H., Koh, Y., Han, J., Rim, Y. A., Nam, Y., & Ju, J. H. (2025) · Stem Cell Research & Therapy · doi:10.1186/s13287-025-04825-1 · Cited by 2
“Patient-specific iPSC lines allow correction of pathogenic HBB variants and re-testing of erythroid maturation in isogenic backgrounds, while genome editing strategies reactivating fetal programs have matured from concept to clinic [201–204].”
Targeting RUNX1 Germline Variants: Agents Under Investigation
Ghalamkari, S., Hahn, C. N., Lau, A., Scott, H. S., Homan, C. C., & Brown, A. L. (2025) · Current Hematologic Malignancy Reports · doi:10.1007/s11899-025-00767-w · Cited by 1
“Proof-of-concept was demonstrated through clinical trials involving thalassemia and sickle cell disease, providing compelling evidence that this approach can successfully mitigate hematological defects [32 , 33].”
Fetal Hemoglobin Research and Clinical Relevance in Sickle Cell Disease
Gudmundsdóttir, B. K., & Tisdale, J. F. (2025) · Physiology · doi:10.1152/physiol.00024.2025 · Cited by 1
Rising Star Engineering the Genome for Curative Futures
Li, D. (2026) · Journal of Molecular Biology · doi:10.1016/j.jmb.2025.169618 · Cited by 1
An intergenic silencer region regulates HBG expression
Zhu, X., Liu, L., Li, Y., Takezaki, M., Bombin, S., Yu, A., Pendergast, M. A., Sheehan, V., Kuppers, D. A., Bleris, L. G., et al. (2026) · Blood Red Cells & Iron · doi:10.1016/j.brci.2026.100046 · Cited by 1
Koren, A., Levin, C., Livshits, L., Valeri, F., Peretz, S., Raz, S., Bogdanova, A. Y., & Gassmann, M. (2026) · HemaSphere · doi:10.1002/hem3.70278 · Cited by 1
Gab-Obinna, C. L., Oriaku, I., Okeoma, O. I., Olowookere, A. K., Obong, E. E., Onyedum, N. N., & Bala, J. I. (2026) · Australian Journal of Biomedical Research · doi:10.63946/aubiomed/17736 · Cited by 2
“Gene addition studies without genome editing were also excluded [36].”
Alotaibi, D., Aldagdog, F., Alramadhan, S. I., Almuhaidib, B., Asiri, N., Almodhi, L., Alshabaan, M., Alborhan, R., Vatte, C., Mohiuddin, S. S., et al. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27031203 · Cited by 2
“Compared with ex vivo autologous HSC gene therapy, which requires stem cell harvesting, ex vivo manipulation, reinfusion, and conditioning regimens, such as myeloab-lation, that can cause substantial toxicity and limit broad applicability [79,81].”
Complex HBB gene editing outcomes revealed by a fluorescent reporter cell model
Karsenty, C. L., Betancourth, D., Cao, M., Pham, Q.-K., Park, S. H., & Bao, G. (2026) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2026.102854 · Cited by 1
Ren, Y., Xu, J., Luo, Q., Li, P., Jiang, M., Cheng, Y., Zhang, H., Wei, D., Bai, W., Liu, S., et al. (2026) · ACS Nano · doi:10.1021/acsnano.5c17709 · Cited by 1
Kim, Y.-J., Bang, S., & Chung, A. J. (2026) · Small · doi:10.1002/smll.202512553 · Cited by 1
“Intracellular delivery of CRISPR components has traditionally relied on electroporation, favored for its operational simplicity and relatively high transfection efficiency [33, 34].”
Therapeutic Gene Editing: DNA Repair Pathways, Emerging Editors, and Clinical Progress
Tsai, L., Xiong, Y., Liu, D., Yang, D., Zhang, J., Xu, J., Han, R., & Chen, Y. (2026) · iNew Medicine · doi:10.1002/inm3.70018 · Cited by 1
Self-citationPrecision Is Not Enough: When Tools Outpace Translation in Ocular Gene Therapy
Elsayed, M. E. A. A., & MacLaren, R. E. (2026) · Genes · doi:10.3390/genes17030283 · Cited by 1
“…autotemcel) for sickle cell disease marked the first regulatory endorsement in the United States of a CRISPR-based therapeutic modality, and it built on years of clinical experience showing that editing hematopoietic stem cells can yield sustained clinical benefit in hemoglobinopathies [119,120].”
Yin, J., Wen, H., Zeng, J., Sun, Y., Chen, X., Jin, L. G., Song, Y., & Xia, S. (2026) · Biology of Reproduction · doi:10.1093/biolre/ioag056 · Cited by 1
CRISPR in Thalassemia: Global Research Trend Analysis
Saboor, M., Alblooshi, M. J., Alkaabi, A. A., Soozaei, F. R., & Alketbi, M. H. (2026) · Hemoglobin · doi:10.1080/03630269.2026.2634815 · Cited by 1
“The highest citation count was observed for the 2021 New England Journal of Medicine report on CRISPR–Cas9 therapy for SCD and β-thalassemia ( n = 1,389) [26].”
CRISPR and genome editing: precision tools for personalized therapies
Ranga, P. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-40483-2.00047-9 · Cited by 1
Contieri, M., Gatta, F., Colonnese, M., et al. (2026) · Drugs - Real World Outcomes · doi:10.1007/s40801-026-00545-x · Cited by 1
“There has been promising evidence from gene therapy studies [13–15], which are now coming to the market in Europe.”
CRISPR: Revolutionizing genetic science and ethics
Singh, H., Goel, B., Shekhar, S., Singh, R., & Garg, C. (2026) · Next research. · doi:10.1016/j.nexres.2026.101669 · Cited by 1
Lanzkron, S., Coleman‐Cowger, V. H., Thompson, A. A., Carroll, C. P., Clemons, T. E., DeBaun, M. R., Kanter, J., Malik, P., Manwani, D. G., Pierciey, F. J., et al. (2026) · Blood Advances · doi:10.1182/bloodadvances.2025019400 · Cited by 1
“11,12,13 The focus of the Physical Examination and Medical History WG was to define the basic framework of data to be collected for clinical studies in SCD.”
CRISPR-Cas at a crossroads: from microbial immunity to precision biotechnology
Eliwa, A. I. A., & Eldahshan, M. M. (2026) · Journal of Immunoassay and Immunochemistry · doi:10.1080/15321819.2026.2658465 · Cited by 2
“[36] Box 1.”
From edits to Circuits: Nucleic acid therapeutics for Correcting human disease
Guinn, M. T., Sinenko, I., Ghanta, R. K., & Omid Veiseh, A. (2026) · Materials Today · doi:10.1016/j.mattod.2026.103351 · Cited by 1
Fourth-generation gene editors: Integration-based genome engineering
Kincaid, A. E., Hewitt, A. W., & Rajendra, K. C. (2026) · Molecular Therapy Advances · doi:10.1016/j.omta.2026.201753 · Cited by 2
“29,30 Base editing technologies have also taken significant steps toward clinical testing, with early therapeutic programs targeting hematologic and genetic diseases and currently are in phase 1/2 clinical trials.”
Pratumkaew, P., Wattanapanitch, M., Viprakasit, V., et al. (2026) · Stem Cell Research & Therapy · doi:10.1186/s13287-026-05057-7 · Cited by 1
Adedokun, K. A., Fayemo, H. T., Oyeniyi, G. M., Bello, A., Orugun, O. A., Imodoye, S. O., Ogunlakin, A. D., Eziagu, U. B., Dewan, S. M. R., Khan, S. A., et al. (2026) · Next Materials · doi:10.1016/j.nxmate.2026.102232 · Cited by 2
Makhijani, S., Alasiri, G. A., Quadri, M. S. A., & Ingle, R. G. (2026) · Discover Nano · doi:10.1186/s11671-026-04653-z · Cited by 4
“GE treatments employ single-dose infusion and genome-edited ex vivo hematopoietic stem cells from patients via CRISPR-Cas9 technology [123].”
Naoe, Y., Fujimoto, N., Makita, Y., Li, D., Inukai, N., & Hotta, A. (2026) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2026.102958 · Cited by 1
“23,63,64 In conclusion, by combining high-sensitivity in silico nomination, unbiased in vitro cleavage mapping, isogenic iPSC WGS with in-del-cluster features, and targeted amplicon sequencing, we present a conservative, scalable path to off-target risk assessment for LNP-delivered CRISPR therapies.”
Wallman, D. J., Koç-Günel, S., Hynds, R. E., Ryan, A. L., & Olmer, R. (2026) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00092.2026 · Cited by 1
Zhou, X., K, T., Ding, X., Luo, Z., Yin, C., & Lu, Z. (2026) · Frontiers in Medicine · doi:10.3389/fmed.2026.1872028 · Cited by 1
Clinical pharmacology insights from recent cell and gene therapy approvals relevant to pediatrics
Kunanayagam, S., Wang, M. C., Loucks, C. M., García‐Bournissen, F., Verstegen, R. H. J., & Lewis, T. R. (2026) · Pediatric Research · doi:10.1038/s41390-026-05138-6 · Cited by 1
Gen-Doping: aktuelle Nachweisverfahren und analytische Herausforderungen
Thevis, M., Thomas, A., & Naumann, N. (2026) · Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz · doi:10.1007/s00103-026-04257-z · Cited by 1
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-09-27, under version 3 of the claim definition (prompt extract-v3).
A second model labelled each claim on 2026-09-27 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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