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
23 Own result · 7 Partly supported · 5 Own interpretation · 4 Supported · 2 Supported so far · 2 Own method · 1 No full text of the sources · 1 Not checked yet · 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)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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
hedgedconditionalSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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).”
plaindirectSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“After the administration of CTX001, high levels of edited alleles in bone marrow CD34+ cells and nucleated peripheral-blood cells were maintained (Table 1).”
plaindirectSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“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).”
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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.”
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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).”
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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).”
plaindirectSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“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.”
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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).”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“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.”
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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).”
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“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.”
plainn = 10- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“The CTX001 drug product had an allelic editing frequency of 68.9%.”
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“Four other enrolled patients with SCD withdrew from the study before being treated with CTX001 (Table S16).”
plainn = 4- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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.”
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“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).”
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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).”
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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.”
hedgedconditionalSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“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.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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.”
plaindirectn = 2- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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.”
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
Cites
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BCL11A enhancer dissection by Cas9-mediated in situ saturating mutagenesis
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Gene therapy in a patient with sickle cell disease
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Self-citationGene Therapy in Patients with Transfusion-Dependent β-Thalassemia
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An Erythroid Enhancer of BCL11A Subject to Genetic Variation Determines Fetal Hemoglobin Level
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Cited by
Sorted by citations
Items 1,701–1,800 of 1,950
CRISPR's impact on cancer: From fundamental models to clinical solutions
Hillary, V. E., Rajan, V., & Ceasar, S. A. (2025) · Life Sciences · doi:10.1016/j.lfs.2025.124087
PETRA: Prime editing of transcribed regulatory elements to assay expressionPreprint
Armas, M., Herger, M., Cubitt, L., & Findlay, G. M. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.11.18.689114
Demystifying Gene-Based Therapies in Pediatric Health Care
Tinkle, M. B., & Schluter, W. (2025) · The Journal for Nurse Practitioners · doi:10.1016/j.nurpra.2025.105611
β-Nicotinamide mononucleotide: a novel broad-spectrum CRISPR inhibitorPreprint
Wei, T., Shen, W., Li, W., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.11.22.685598
Trajectory of genome editing technology
Luo, Y., Ceasar, S. A., & Benabdellah, K. (2025) · BMC Biology · doi:10.1186/s12915-025-02450-1 · Cited by 1
Herrera, R. J., & Garcia‐Bertrand, R. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-28919-4.00002-7
Ryu, Y. C., Bao, G., & Hwang, B. H. (2025) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2025.118838
Santana, M. V. D. O., Marchiori, C. H., Malheiros, K. D. P., & de Melo, È. M. (2025) · Journal of Biology and Medicine · doi:10.17352/jbm.000048
Molecular mastery: Harnessing DNA technology for disease prevention
Dornadula, G., Ramakrishna, C., Shaik, S. B., Meriga, P. K., Chintha, L., Gurugari, Y., D., K., Shaik, S. F., & Cheong, S. H. (2025) · Genes & Diseases · doi:10.1016/j.gendis.2025.101976
Potency of human hematopoietic cells from a novel CD34+ isolation technique
Ropa, J. P., Park, J., Newton, J., Kim, S. J., Park, Y., Messer, J. G., Blacher, J., & Namin, S. M. (2025) · Stem Cells Translational Medicine · doi:10.1093/stcltm/szaf067
Engineered AcrIIA5 for optogenetic control of CRISPR‐Cas9‐based genome editing
Chen, Q., Yao, J., Lu, Y., Qiu, R., Deng, Z., & Sun, Y. (2025) · mLife · doi:10.1002/mlf2.70016 · Cited by 1
“Notably, the Class 2 type II CRISPR system, which utilizes a single effector Cas9 protein with guide RNA (gRNA) to target speci fi c gene loci, has been applied in the fi elds of genetic disease treatment 5 – 7 , epigenetic modi fi cations 8 – 10 , and transcriptional regulation 11 – 13 .”
Djaya, N., Vanessa, I., & Soekiono, C. J. (2025) · Journal Of Tropical Pharmacy And Chemistry · doi:10.30872/jtpc.v9i2.310
Deneault, É. (2025) · Genetics. · doi:10.5772/intechopen.1013143 · Cited by 1
Investigating and correcting a rare pathogenic mutation in GDF11
Congdon, S. T., Bennett, J. E., Opinya, R., Agosto, A. R., Dossias, O., Kokko, C., Levesque, A. A., Koob, A. O., Silver, A. C., & Thomas-Charles, C. A. (2025) · Human Genetics and Genomics Advances · doi:10.1016/j.xhgg.2025.100559
“…Vertex and CRISPR Therapeutics and approved in 2023 for the treatment of sickle cell disease (Hemoglobin subunit beta [HBB; MIM: 141900) and transfusion-dependent β -thalassemia (HBB; MIM: 141900) 2,3 ; as well as Intellia’s NTLA-2001, for individuals with transthyretin amyloidosis (MIM: 176300).”
Kwon, J., Kim, M., Hwang, W., Jo, A., Hwang, G.-H., Jung, M., Kim, U. G., Cui, G., Kim, H. S., Eom, J.-H., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22601900
Im, S. H., Jang, M., Park, J.-H., & Chung, H. J. (2024) · Figshare · doi:10.6084/m9.figshare.25596399
Bloszyk, J., Stachowiak, M., & Halliday, B. (2006) · INFM-OAR (INFN Catania) · doi:10.5281/zenodo.172508
Jiang, J., Chen, Y., Zhang, L., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20501879
Self-citationAdditional file 1 of Decision-making about gene therapy in transfusion dependent thalassemia
Quarmyne, M.-O., Ross, D. C., Sinha, C. B., Bakshi, N., Boudreaux, J. M., & Krishnamurti, L. (2022) · Figshare · doi:10.6084/m9.figshare.21077409
Kwon, J., Kim, M., Hwang, W., Jo, A., Hwang, G.-H., Jung, M., Kim, U. G., Cui, G., Kim, H. S., Eom, J.-H., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22601891
Zhao, J.-J., Sun, X.-Y., Tian, S.-N., Zhao, Z.-Z., Yin, M.-D., Zhao, M., Zhang, F., Li, S.-A., Yang, Z.-X., Wen, W., et al. (2024) · Figshare · doi:10.6084/m9.figshare.25239456
Leung, A. O.-W., Yiu, T.-C., Liu, L., Tam, H.-Y., Gu, S., Tu, J., Pei, D., & Cheung, H.-H. (2023) · Figshare · doi:10.6084/m9.figshare.22614614
Additional file 1 of Global analysis of suppressor mutations that rescue human genetic defects
Ünlü, B., Pons, C., Ho, U. L., Batté, A., Aloy, P., & van Leeuwen, J. (2023) · Figshare · doi:10.6084/m9.figshare.24295598
Kwon, J., Kim, M., Hwang, W., Jo, A., Hwang, G.-H., Jung, M., Kim, U. G., Cui, G., Kim, H. S., Eom, J.-H., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22601906
Zhao, J.-J., Sun, X.-Y., Tian, S.-N., Zhao, Z.-Z., Yin, M.-D., Zhao, M., Zhang, F., Li, S.-A., Yang, Z.-X., Wen, W., et al. (2024) · Figshare · doi:10.6084/m9.figshare.25239409
Kwon, J., Kim, M., Hwang, W. C., Jo, A., Hwang, G.-H., Jung, M., Kim, U. G., Cui, G., Kim, H. S., Eom, J.-H., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22601897
Additional file 2 of Global analysis of suppressor mutations that rescue human genetic defects
Ünlü, B., Pons, C., Ho, U. L., Batté, A., Aloy, P., & van Leeuwen, J. (2024) · Figshare · doi:10.6084/m9.figshare.24295736
Beyond HbS and Thalassemia: CRISPR-Cas9 Strategies for Targeting Rare Hemoglobin Gene MutationsPreprint
Ahsan, M. (2026) · Research Square · doi:10.21203/rs.3.rs-10709958/v1
Potentiality of advanced nanomaterial based on microorganisms for regenerative medicine
Ritu, Gulia, S., Singh, S., Majhi, K., Panchal, P., Das, A., & Chandra, P. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-31526-8.00003-0 · Cited by 1
Breakthroughs in Stem Cell-Based Treatments for ALS and FTD: Promises and Challenges Ahead
Frederiksen, H. R. S., & Freude, K. (2025) · Stem cell biology and regenerative medicine · doi:10.1007/978-3-031-94101-6_7
Cai, M. (2025) · Dinkum Journal of Medical Innovations · doi:10.71017/djmi.4.7.d-0455
Enfoque terapéutico de la anemia falciforme
Soto-Manzano, A. V., Córdoba-García, S., Castaño, L. M. F., Uribe-Ramírez, M., & Sánchez, L. M. M. (2025) · Revista Repertorio de Medicina y Cirugía · doi:10.31260/repertmedcir.01217372.1553
Sandhya, S., Prakash Goudanavar, S. O. P., & Naik, P. (2025) · International Journal of Peptide Research and Therapeutics · doi:10.1007/s10989-025-10779-y
“These cases high-light how transforming CRISpen is for precision medicine (Frangoul et al. 2021; Sharma et al. 2023; Longhurst et al. 2024)While RNA-based treatments like siRNA and mRNA are attracting interest for their precision and reversibility, CRISpen promises permanent gene repair.”
Disrupting epigenetic insulation underlies CRISPR therapy for β-hemoglobinopathies
Wang, K., Wang, J., Weiss, M. J., Yue, F., & Xu, J. (2025) · Molecular Therapy · doi:10.1016/j.ymthe.2025.12.015
Sickle Cell Disease: Treatment Options of the Past, Present, and Future
Jacobs, C., & Liu, A. (2025) · AJN American Journal of Nursing · doi:10.1097/ajn.0000000000000216
CRISPR-HAWK: Haplotype- and Variant-Aware Guide Design Toolkit for CRISPR-CasPreprint
Kumbara, A., Tognon, M., Carone, G., Fontanesi, A., Bombieri, N., Giugno, R., & Pinello, L. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2025.12.27.696698
“Casgevy (exagamglogene autotemcel), one of the first FDA-approved CRISPR therapies for sickle cell disease and beta-thalassemia, relies on precise editing of the BCL11A enhancer using guide sg1617 (Frangoul et al., 2021).”
Advances of Genomic Medicine in Neurodevelopmental Disorders
Akter, H., Uddin, M. J., & Nabi, A. H. M. N. (2026) · Interdisciplinary biotechnological advances · doi:10.1007/978-981-95-3612-2_6
CRISPR-Cas9 Technology for Combating Genetic Disorders
Sharma, A. K., & Singh, P. (2026) · IGI Global eBooks · doi:10.4018/979-8-3373-4857-5.ch005
Self-citationCRISPR-Cas9 Technology in Regenerative Medicine and Tissue Engineering
Gunasekaran, A., Vanaraj, M., Kumar, M. S. P., et al. (2026) · IGI Global eBooks · doi:10.4018/979-8-3373-4857-5.ch006
Iterative engineering of a compact Cas9 ortholog for in vivo gene editing via single AAV deliveryPreprint
Barenghi, A., Hackett, J. A., Humphreys, N. E., & Sawitzke, J. A. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.01.12.698990
“Collectively, these CRISPR-derived technologies have had a transformative impact across basic research, agriculture and medicine, with therapeutic applications now advancing into clinical development and patients [4-8].”
Modern therapeutic approaches for β-thalassemia: from blood transfusion to gene therapy
Dolgushina, E. N., Коптева, О. С., Shakirova, A. L., Lepik, K. V., Bykova, T. A., Zubarovskaya, L. S., & Kulagin, A. (2026) · Russian Journal of Pediatric Hematology and Oncology · doi:10.21682/2311-1267-2025-12-3-56-67
Gene-Editing-Based Approaches for Curing Sickle Cell Disease
Park, S. H., Karsenty, C. L., Prasca-Chamorro, D., Moyo, B., Yoo, B., & Bao, G. (2026) · Springer eBooks · doi:10.1007/978-3-032-12532-3_8
Caruso, C. M., & Lam, W. A. (2026) · Springer eBooks · doi:10.1007/978-3-032-12532-3_3
Hemoglobin: A Target for Sickle Cell Disease Drug Discovery
Donkor, A. K., Opare, A., Thomas, W., Abdulmalik, O. Y., Zhang, Y., & Safo, M. K. (2026) · Springer eBooks · doi:10.1007/978-3-032-12532-3_10
Bibliometric Insights into CRISPR-Cas9 Research Targeting Human Disease Pathology
Sweileh, M. W. (2026) · SAGE Open · doi:10.1177/21582440261415669
Global research landscape of inborn errors of immunity: a bibliometric analysis (1991–2025)
Wu, Q., Gao, J., Yuan, Y., Yang, H., & Fu, Q. (2026) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-025-04191-4 · Cited by 1
“Examples include: The first CRISPR/Cas9-based therapy (Exa-cel) for hemoglobinopathies [17, 18]; The first prime editor therapy (PM359) in CGD trials (NCT06559176) [16]; The first personalized in vivo base-editing treatment [19]; These advances offer ultimate hope for curing IEI patients and…”
CRISPR-Based Synthetic Gene Circuits for Industrial and Therapeutic Applications
Raue, J. M. (2024) · Academic International Journal of Engineering Science · doi:10.59675/e224
“CRISPR systems have been used in gene therapy to repair genetic pathogen mutations in genetic disease treatments such as sickle cell anemia, beta-thalassemia, and Duchenne muscular dystrophy with a number of therapeutic candidates successfully passing through clinical development stages [47, 48].”
Agarwal, S., Kumar, S., Prabhan, S. S., et al. (2026) · Hemoglobin · doi:10.1080/03630269.2026.2612972
“A widespread newborn screening for their prevention is the need of the hour, along with measures to increase public awareness and timely counseling of at-risk individuals or couples for prenatal diagnosis, thereby reducing the disease burden [27–30].”
Ginder, G. D., Shang, S., & Williams, D. C. (2026) · Blood · doi:10.1182/blood.2025031153 · Cited by 1
Steinberg, M. H. (2026) · Springer eBooks · doi:10.1007/978-3-031-96019-2_34
Self-citationShibah, S. R. M. (2026) · SSRN Electronic Journal · doi:10.2139/ssrn.6122246
Bio-orthogonal chemistry-based strategy to Turn-OFF CRISPR-Cas9 activity in solution and live cells
Pandit, B., Vangaveti, S., Sentre, J. F., McClain, I. M., Fuchs, G., & Royzen, M. (2026) · NAR Molecular Medicine · doi:10.1093/narmme/ugag008
“Perhaps the most striking biomedical breakthrough has been in the treatment of sickle cell disease, the most common inherited hemoglobinopathy worldwide [ 6 , 7 ].”
Near completely reversing the γ- to β-globin switch by enhancer release, retargeting and reinforcingPreprint
Wang, N., Yang, K., Xie, X., Cui, S., Pei, X., Zhao, X., Hao, D., Jia, Y., Yang, G., Liu, R., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.01.30.702713
Cell and Gene Therapy in Equine Ocular Disease
Young, K. A. S., Schnabel, L. V., & Gilger, B. C. (2026) · Veterinary Ophthalmology · doi:10.1111/vop.70151
Sharma, P., & Mishra, P. (2026) · Indian Journal of Hematology and Blood Transfusion · doi:10.1007/s12288-026-02337-3
LDB1 represses fetal hemoglobin expression by enhancing BCL11A transcription
Park, S.-W., Choi, C., Park, I.-B., Kang, S. J., Lee, H. J., Kim, J.-I., Bae, J., Geum, D., Cheon, Y. P., & Chun, T. (2026) · Redox Biology · doi:10.1016/j.redox.2026.104070
Exploring gene editing as a potential therapeutic strategy for hemophilia
Kumarasamy, N., & Balakrishnan, B. (2026) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2026.1727204
CRISPR-Cas9 Teknolojisi: Biyoteknolojide Devrim Niteliğinde Bir İnovasyon
Özanatça, L., & Işık, R. (2025) · DergiPark (Istanbul University)
Luo, S., Lin, L., Zhang, H., Yang, Y., Liu, Y., Han, Y., Chen, F., Liang, R., Niang, X., Dai, J., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.02.02.703403
Virus-like particle delivery enables orthogonal genome editing in vitro and in vivoPreprint
Shin, S., Nam, B.-G., Park, E. J., Kim, M. G., Cho, C. S., Kim, Y.-W., Lee, S., Kim, J. H., & Sangsu, B. A. E. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.02.10.705092 · Cited by 1
Integrating Genetics and Molecular Biology into Routine Clinical Care
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Casgevy: A Turning Point in Genetic MedicinePreprint
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CRISPR-Cas9: Genome Engineering and Future Vaccine Applications
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“…ex vivo editing of hematopoietic stem cells (for SCD/TDT) shows transformative efficacy (approximately 90% resolution of vaso-occlusive crises) [93], in vivo systemic delivery (for ATTR) achieves robust biomarker reduction but requires careful dose optimization to balance efficacy with…”
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Exploring the latest emerging drugs for the treatment of sickle cell disease
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“14 17 For example, the approval of Casgevy (exagamglo-gene autotemcel) for sickle cell disease and β -thalassemia marks the first clinical translation of targeted HSC engineering by genome editing, establishing a foundation for next-generation therapies.”
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“The CRISPR-Cas9 study of the BCL11A erythroid enhancer reports outcomes in only two patients and explicitly acknowledges limitations, including lack of clonal diversity analysis and uncertainty regarding long-term stem cell behavior and broader applicability [ 6 ] .”
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Self-citationRecent Advancements in Gene Therapy
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“While gene therapies avoid the need for compatible donors, they share many of the same limitations as HSCT [26, 27].”
Genetic variants in pulmonary hypertension associated with chronic obstructive pulmonary disease
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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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