Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Advances in genome editing: the technology of choice for precise and efficient β-thalassemia treatment

Gene Therapy volume 28, pages 6–15 (2021)Cite this article

Subjects

Abstract

Beta (β)-thalassemia is one of the most significant hemoglobinopathy worldwide. The high prevalence of the β-thalassemia carriers aggravates the disease burden for patients and national economies in the developing world. The survival of β-thalassemia patients solely relies on repeated transfusions, which eventually results into multi-organ damage. The fetal γ-globin genes are ordinarily silenced at birth and replaced by the adult β-globin genes. However, mutations that cause lifelong persistence of fetal γ-globin, ameliorate the debilitating effects of β-globin mutations. Therefore, therapeutically reactivating the fetal γ-globin gene is a prime focus of researchers. CRISPR/Cas9 is the most common approach to correct disease causative mutations or to enhance or disrupt the expression of proteins to mitigate the effects of the disease. CRISPR/cas9 and prime gene editing to correct mutations in hematopoietic stem cells of β-thalassemia patients has been considered a novel therapeutic approach for effective hemoglobin production. However, genome-editing technologies, along with all advantages, have shown some disadvantages due to either random insertions or deletions at the target site of edition or non-specific targeting in genome. Therefore, the focus of this review is to compare pros and cons of these editing technologies and to elaborate the retrospective scope of gene therapy for β-thalassemia patients.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Gene Editing and β-thallasemia.
Fig. 2: The Human Globin Locus and Its Developmental Regulation.
Fig. 3: Summary of genome-editing strategies and known molecular mechanisms within the β-globin locus.

Similar content being viewed by others

References

  1. Weatherall D, Akinyanju O, Fucharoen S, Olivieri N, Musgrove P. Inherited disorders of hemoglobin. Oxford University Press. 2006; Chapter 34.

  2. Cousens NE, Gaff CL, Metcalfe SA, Delatycki MB. Carrier screening for beta-thalassaemia: a review of international practice. Eur J Hum Genet. 2010;18:1077–83.

    PubMed  PubMed Central  Google Scholar 

  3. Manzoor I, Zakar R. Sociodemographic determinants associated with parental knowledge of screening services for thalassemia major in Lahore. Pak J Med Sci. 2019;35:483–8.

    PubMed  PubMed Central  Google Scholar 

  4. Weatherall DJ. Thalassaemia: the long road from bedside to genome. Nat Rev Genet. 2004;5:625–31.

    CAS  PubMed  Google Scholar 

  5. Yasmeen H, Hasnain S. Epidemiology and risk factors of transfusion transmitted infections in thalassemia major: a multicenter study in Pakistan. Hematol Transfus Cell Ther. 2019;41:316–23.

  6. Kanwal S, Bukhari S, Perveen S. Molecular genetics and prenatal diagnosis of beta thalassemia to control transfusion dependent births in carrier Pakistani couples. J Pak Med Assoc. 2010;67:1030–4.

    Google Scholar 

  7. Tehreem Tanveer HM, Butt ZA. Butt are people getting quality thalassemia care in twin cities of Pakistan? A comparison with international standards. Int J Qual Health Care. 2018;30:200–7.

    PubMed  Google Scholar 

  8. Levine L, Levine M. Health care transition in thalassemia: pediatric to adult-oriented care. Ann N Y Acad Sci. 2010;1202:244–7.

    PubMed  Google Scholar 

  9. Ngo DA, Aygun B, Akinsheye I, Hankins JS, Bhan I, Luo HY, et al. Fetal haemoglobin levels and haematological characteristics of compound heterozygotes for haemoglobin S and deletional hereditary persistence of fetal haemoglobin. Br J Haematol. 2012;156:259–64.

    CAS  PubMed  Google Scholar 

  10. Lavelle D, Engel JD, Saunthararajah Y. Fetal hemoglobin induction by epigenetic drugs. Semin Hematol. 2018;55:60–7.

    PubMed  PubMed Central  Google Scholar 

  11. Akinsheye I, Alsultan A, Solovieff N, Ngo D, Baldwin CT, Sebastiani P, et al. Fetal hemoglobin in sickle cell anemia. Blood. 2011;118:19–27.

  12. Ware RE. How I use hydroxyurea to treat young patients with sickle cell anemia. Blood. 2010;115:5300–11.

  13. Li Q, Peterson KR, Fang X, Stamatoyannopoulos G. Locus control regions. Blood. 2002;100:3077–86.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Ikawa Y, Miccio A, Magrin E, Kwiatkowski JL, Rivella S, Cavazzana M. Gene therapy of hemoglobinopathies: progress and future challenges. Hum Mol Genet. 2019;28:R24–30.

    CAS  PubMed  Google Scholar 

  15. Sankaran VG, Weiss MJ. Anemia: progress in molecular mechanisms and therapies. Nat Med. 2015;21:221–30.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Miller IJ, Bieker JJ. A novel, erythroid cell-specific murine transcription factor that binds to the CACCC element and is related to the Krüppel family of nuclear proteins. Mol. Cell Biol. 1993;13:2776–86.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Lettre G, Sankaran VG, Bezerra MA, Araujo AS, Uda M, Sanna S, et al. DNA polymorphisms at the BCL11A, HBS1L-MYB, and beta-globin loci associate with fetal hemoglobin levels and pain crises in sickle cell disease. Proc Natl Acad Sci USA. 2008;105:11869–74.

    CAS  PubMed  Google Scholar 

  18. Uda M, Galanello R, Sanna S, Lettre G, Sankaran VG, Chen W, et al. Genome-wide association study shows BCL11A associated with persistent fetal hemoglobin and amelioration of the phenotype of beta-thalassemia. Proc Natl Acad Sci USA. 2008;105:1620–5.

    CAS  PubMed  Google Scholar 

  19. Bauer DE, Kamran SC, Lessard S, Xu J, Fujiwara Y, Lin C, et al. An erythroid enhancer of BCL11A subject to genetic variation determines fetal hemoglobin level. Science. 2013;342:253–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Funnell AP, Prontera P, Ottaviani V, Piccione M, Giambona A, Maggio A, et al. 2p15-p16.1 microdeletions encompassing and proximal to BCL11A are associated with elevated HbF in addition to neurologic impairment. Blood. 2015;126:89–93.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Xu J, Sankaran VG, Ni M, Menne TF, Puram RV, Kim W, et al. Transcriptional silencing of {gamma}-globin by BCL11A involves long-range interactions and cooperation with SOX6. Genes Dev. 2010;24:783–98.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Masuda T, Wang X, Maeda M, Canver MC, Sher F, Funnell AP, et al. Transcription factors LRF and BCL11A independently repress expression of fetal hemoglobin. Science. 2016;351:285–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Garner C, Tatu T, Reittie JE, Littlewood T, Darley J, Cervino S, et al. Genetic influences on F cells and other hematologic variables: a twin heritability study. Blood. 2000;95:342–6.

    CAS  PubMed  Google Scholar 

  24. Menzel S, Garner C, Gut I, Matsuda F, Yamaguchi M, Heath S, et al. A QTL influencing F cell production maps to a gene encoding a zinc-finger protein on chromosome 2p15. Nat Genet. 2007;39:1197–9.

    CAS  PubMed  Google Scholar 

  25. Sankaran VG, Menne TF, Xu J, Akie TE, Lettre G, Van Handel B, et al. Human fetal hemoglobin expression is regulated by the developmental stage-specific repressor BCL11A. Science. 2008;322:1839–42.

    CAS  PubMed  Google Scholar 

  26. Xu J, Bauer DE, Kerenyi MA, Vo TD, Hou S, Hsu YJ, et al. Corepressor-dependent silencing of fetal hemoglobin expression by BCL11A. Proc Natl Acad Sci USA. 2013;110:6518–23.

    CAS  PubMed  Google Scholar 

  27. Lettre G, Bauer DE. Fetal haemoglobin in sickle-cell disease: from genetic epidemiology to new therapeutic strategies. Lancet. 2016;387:2554–64.

    CAS  PubMed  Google Scholar 

  28. Wu Y, Zeng J, Roscoe BP, Liu P, Yao Q, Lazzarotto CR, et al. Highly efficient therapeutic gene editing of human hematopoietic stem cells. Nat Med. 25:776–83.

  29. Bunn HF. Pathogenesis and treatment of sickle cell disease. N Engl J Med. 1997;337:762–9.

    CAS  PubMed  Google Scholar 

  30. Sankaran VG, Nathan DG. Thalassemia: an overview of 50 years of clinical research. Hematol Oncol Clin North Am. 2010;24:1005–20.

    PubMed  Google Scholar 

  31. Wilber A, Hargrove PW, Kim YS, Riberdy JM, Sankaran VG, Papanikolaou E, et al. Therapeutic levels of fetal hemoglobin in erythroid progeny of beta-thalassemic CD34+ cells after lentiviral vector-mediated gene transfer. Blood. 2011;117:2817–26.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Zhao Q, Zhou W, Rank G, Sutton R, Wang X, Cumming H, et al. Repression of human gamma-globin gene expression by a short isoform of the NF-E4 protein is associated with loss of NF-E2 and RNA polymerase II recruitment to the promoter. Blood. 2006;107:2138–45.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Ippolito GC, Dekker JD, Wang YH, Lee BK, Shaffer AL 3rd, Lin J, et al. Dendritic cell fate is determined by BCL11A. Proc Natl Acad Sci USA. 2014;111:E998–1006.

    CAS  PubMed  Google Scholar 

  34. Liu P, Keller JR, Ortiz M, Tessarollo L, Rachel RA, Nakamura T, et al. Bcl11a is essential for normal lymphoid development. Nat Immunol. 2003;4:525–32.

    CAS  PubMed  Google Scholar 

  35. Luc S, Huang J, McEldoon JL, Somuncular E, Li D, Rhodes C, et al. Bcl11a deficiency leads to hematopoietic stem cell defects with an aging-like phenotype. Cell Rep. 2016;16:3181–94.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Sankaran VG, Xu J, Ragoczy T, Ippolito GC, Walkley CR, Maika SD, et al. Developmental and species-divergent globin switching are driven by BCL11A. Nature. 2009;460:1093–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Xu J, Peng C, Sankaran VG, Shao Z, Esrick EB, Chong BG, et al. Correction of sickle cell disease in adult mice by interference with fetal hemoglobin silencing. Science. 2011;334:993–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Esteghamat F, Gillemans N, Bilic I, van den Akker E, Cantu I, van Gent T, et al. Erythropoiesis and globin switching in compound Klf1::Bcl11a mutant mice. Blood. 2013;121:2553–62.

    CAS  PubMed  Google Scholar 

  39. Platt OS, Orkin SH, Dover G, Beardsley GP, Miller B, Nathan DG. Hydroxyurea enhances fetal hemoglobin production in sickle cell anemia. J Clin Invest. 1984;74:652–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Thornburg CD, Files BA, Luo Z, et al. Impact of hydroxyurea on clinical events in the BABY HUG trial. Blood. 2012;120:4304–10.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Kinney TR, Helms RW, O’Branski EE, Ohene-Frempong K, Wang W, Daeschner C, et al. Safety of hydroxyurea in children with sickle cell anemia: results of the HUG-KIDS study, a phase I/II trial. Pediatric Hydroxyurea Group. Blood. 1999;94:1550–4.

    CAS  PubMed  Google Scholar 

  42. Hankins JS, Aygun B, Nottage K, Thornburg C, Smeltzer MP, Ware RE, et al. From infancy to adolescence: fifteen years of continuous treatment with hydroxyurea in sickle cell anemia. Medicine (Baltimore). 2014;93:e215.

    CAS  Google Scholar 

  43. Voskaridou E, Christoulas D, Bilalis A, Plata E, Varvagiannis K, Stamatopoulos G, et al. The effect of prolonged administration of hydroxyurea on morbidity and mortality in adult patients with sickle cell syndromes: results of a 17-year, single-center trial (LaSHS). Blood. 2010;115:2354–63.

    CAS  PubMed  Google Scholar 

  44. Petrillo C, Thorne LG, Unali G, Schiroli G, Giordano AMS, Piras F, et al. Cyclosporine H overcomes innate immune restrictions to improve lentiviral transduction and gene editing in human hematopoietic stem cells. Cell Stem Cell. 2018;23:820–32 e829.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Cavazzana-Calvo M, Payen E, Negre O, Wang G, Hehir K, Fusil F, et al. Transfusion independence and HMGA2 activation after gene therapy of human beta-thalassaemia. Nature. 2010;467:318–22.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Thompson AA, Walters MC, Kwiatkowski J, Rasko JEJ, Ribeil JA, Hongeng S, et al. Gene therapy in patients with transfusion-dependent beta-thalassemia. N Engl J Med. 2018;378:1479–93.

  47. Sii-Felice K, Giorgi M, Leboulch P, Payen E. Hemoglobin disorders: lentiviral gene therapy in the starting blocks to enter clinical practice. Exp Hematol. 2018;64:12–32.

    CAS  PubMed  Google Scholar 

  48. Locatelli FWM, Kwiatkowski JL, Porter J, Sauer MG, Thuret I, Hongeng S, et al. Lentiglobin gene therapy for patients with tranfusion-dependent beta-thalassemia (TDT): results from the phase 3 Northstar-2 and Northstar-3 studies. Blood. 2018;132:1025

    Google Scholar 

  49. Magrin E, Miccio A, Cavazzana M. Lentiviral and genome-editing strategies for the treatment of beta-hemoglobinopathies. Blood. 2019;134:1203–13.

    PubMed  Google Scholar 

  50. Glaser A, McColl B, Vadolas J. The therapeutic potential of genome editing for beta-thalassemia. F1000Res. 2015;4:1–10.

  51. Karponi G, Zogas N. Gene therapy for beta-thalassemia: updated perspectives. Appl Clin Genet. 2019;12:167–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Lee JK, Jeong E, Lee J, Jung M, Shin E, Kim YH, et al. Directed evolution of CRISPR-Cas9 to increase its specificity. Nat Commun. 2018;9:3048.

  53. Cesana D, Ranzani M, Volpin M, Bartholomae C, Duros C, Artus A, et al. Uncovering and dissecting the genotoxicity of self-inactivating lentiviral vectors in vivo. Mol Ther. 2014;22:774–85.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Maeder ML, Gersbach CA. Genome-editing technologies for gene and cell therapy. Mol Ther. 2016;24:430–46.

  55. Genovese P, Schiroli G, Escobar G, Tomaso TD, Firrito C, Calabria A, et al. Targeted genome editing in human repopulating haematopoietic stem cells. Nature. 2014;510:235–40.

  56. Lunardi A, Guarnerio J, Wang G, Maeda T. Pandolfi PP. Role of LRF/pokemon in lineage fate decisions. Blood. 2013;121:2845–53.

  57. Maeda T, Ito K, Merghoub T, Poliseno L, Hobbs RM, Wang G, et al. LRF is an essential downstream target of GATA1 in erythroid development and regulates BIM-dependent apoptosis. Dev Cell. 2009;17:527–40.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Canver MC, Smith EC, Sher F, Pinello L, Sanjana NE, Shalem O, et al. BCL11A enhancer dissection by Cas9-mediated in situ saturating mutagenesis. Nature. 2015;527:192–7.

  59. Chang KH, Smith SE, Sullivan T, Chen K, Zhou Q, West JA, et al. Long-term engraftment and fetal globin induction upon BCL11A gene editing in bone-marrow-derived CD34(+) hematopoietic stem and progenitor cells. Mol Ther Methods Clin Dev. 2017;4:137–48.

  60. Smith EC, Luc S, Croney DM, Woodworth MB, Greig LC, Fujiwara Y, et al. Strict in vivo specificity of the Bcl11a erythroid enhancer. Blood. 2016;128:2338–42.

  61. Vierstra J, Reik A, Chang KH, Stehling-Sun S, Zhou Y, Hinkley SJ, et al. Functional footprinting of regulatory DNA. Nat Methods. 2015;12:927–30.

  62. Metais JY, Doerfler PA, Mayuranathan T, Bauer DE, Fowler SC, Hsieh MM, et al. Genome editing of HBG1 and HBG2 to induce fetal hemoglobin. Blood Adv. 2019;3:3379–92.

    PubMed  PubMed Central  Google Scholar 

  63. Xiong Z, Xie Y, Yang Y, Xue Y, Wang D, Lin S, et al. Efficient gene correction of an aberrant splice site in beta-thalassaemia iPSCs by CRISPR/Cas9 and single-strand oligodeoxynucleotides. J Cell Mol Med. 2019;23:8046–57.

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Traxler EA, Yao Y, Wang YD, Woodard KJ, Kurita R, Nakamura Y, et al. A genome-editing strategy to treat beta-hemoglobinopathies that recapitulates a mutation associated with a benign genetic condition. Nat Med. 2016;22:987–90.

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Khosravi MA, Abbasalipour M, Concordet JP, Berg JV, Zeinali S, Arashkia A, et al. Expression analysis data of BCL11A and gamma-globin genes in KU812 and KG-1 cell lines after CRISPR/Cas9-mediated BCL11A enhancer deletion. Data Brief. 2019;28:104974.

    PubMed  PubMed Central  Google Scholar 

  66. Li J, Lai Y, Shi L. BCL11A down-regulation induces gamma-globin in human beta-thalassemia major erythroid cells. Hemoglobin. 2018;42:225–30.

    CAS  PubMed  Google Scholar 

  67. Kim S, Kim D, Cho SW, Kim J, Kim JS. Highly efficient RNA-guided genome editing in human cells via delivery of purified Cas9 ribonucleoproteins. Genome Res. 2014;24:1012–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Gonzalez-Romero E, Martinez-Valiente C, Garcia-Ruiz C, Vazquez-Manrique RP, Cervera J, Sanjuan-Pla A. CRISPR to fix bad blood: a new tool in basic and clinical hematology. Haematologica. 2019;104:881–93.

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Dever DP, Bak RO, Reinisch A, Camarena J, Washington G, Nicolas CE, et al. CRISPR/Cas9 beta-globin gene targeting in human haematopoietic stem cells. Nature. 2016;539:384–9.

  70. DeWitt MA, Magis W, Bray NL, Wang T, Berman JR, Urbinati F, et al. Selection-free genome editing of the sickle mutation in human adult hematopoietic stem/progenitor cells. Sci Transl Med. 2016;8:360ra134.

    PubMed  PubMed Central  Google Scholar 

  71. Schumann K, Lin S, Boyer E, Simeonov DR, Subramaniam M, Gate RE, et al. Generation of knock-in primary human T cells using Cas9 ribonucleoproteins. Proc Natl Acad Sci USA. 2015;112:10437–42.

    CAS  PubMed  Google Scholar 

  72. Schiroli G, Conti A, Ferrari S, Della Volpe L, Jacob A, Albano L, et al. Precise gene editing preserves hematopoietic stem cell function following transient p53-mediated DNA damage response. Cell Stem Cell. 2019;24:551–565 e558.

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Diez B, Genovese P, Roman-Rodriguez FJ, Alvarez L, Schiroli G, Ugalde L, et al. Therapeutic gene editing in CD34(+) hematopoietic progenitors from Fanconi anemia patients. EMBO Mol Med. 2017;9:1574–88.

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Therapeutics S. A study to assess the safety, tolerability, and efficacy of ST-400 for treatment of transfusion-dependent beta-thalassemia (TDT). US National Library of Medicine: https://clinicaltrials.gov/ct2/show/NCT03432364, 2019.

  75. Incorporated VP. A safety and efficacy study evaluating CTX001 in subjects with transfusion-dependent β-thalassemia. US National Library of Medicine: https://clinicaltrials.gov/ct2/show/NCT03655678, 2020.

  76. Landrum MJ, Lee JM, Benson M, Brown G, Chao C, Chitipiralla S, et al. ClinVar: public archive of interpretations of clinically relevant variants. Nucleic Acids Res. 2016;44:D862–8.

    CAS  PubMed  Google Scholar 

  77. Komor AC, Kim YB, Packer MS, Zuris JA, Liu DR. Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage. Nature. 2016;533:420–4.

  78. Ravindran S. Got mutation? ‘Base editors’ fix genomes one nucleotide at a time. Nature. 2019;575:553–5.

    CAS  PubMed  Google Scholar 

  79. Wienert B, Funnell AP, Norton LJ, Pearson RC, Wilkinson-White LE, Lester K, et al. Editing the genome to introduce a beneficial naturally occurring mutation associated with increased fetal globin. Nat Commun. 2015;6:7085.

    CAS  PubMed  Google Scholar 

  80. Anzalone AV, Randolph PB, Davis JR, Sousa AA, Koblan LW, Levy JM, et al. Search-and-replace genome editing without double-strand breaks or donor DNA. Nature. 2019;576:149–57.

  81. Coleman MB, Adams JG 3rd, Steinberg MH, Plonczynski MW, Harrell AH, Castro O, et al. G gamma A gamma (beta+) hereditary persistence of fetal hemoglobin: the G gamma −158 C–>T mutation in cis to the −175 T–>C mutation of the A gamma-globin gene results in increased G gamma-globin synthesis. Am J Hematol. 1993;42:186–90.

    CAS  PubMed  Google Scholar 

  82. Stoming TA, Stoming GS, Lanclos KD, Fei YJ, Altay C, Kutlar F, et al. An A gamma type of nondeletional hereditary persistence of fetal hemoglobin with a T–C mutation at position -175 to the cap site of the A gamma globin gene. Blood. 1989;73:329–33.

    CAS  PubMed  Google Scholar 

  83. Kim YB, Komor AC, Levy JM, Packer MS, Zhao KT, Liu DR. Increasing the genome-targeting scope and precision of base editing with engineered Cas9-cytidine deaminase fusions. Nat Biotechnol. 2017;35:371–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Rees HA, Liu DR. Publisher correction: Base editing: precision chemistry on the genome and transcriptome of living cells. Nat Rev Genet. 2018;19:801.

    CAS  PubMed  Google Scholar 

  85. Thuronyi BW, Koblan LW, Levy JM, Yeh WH, Zheng C, Newby GA, et al. Publisher correction: Continuous evolution of base editors with expanded target compatibility and improved activity. Nat Biotechnol. 2019;37:1091.

    CAS  PubMed  Google Scholar 

  86. Huang X, Wang Y, Yan W, Smith C, Ye Z, Wang J, et al. Production of gene-corrected adult beta globin protein in human erythrocytes differentiated from patient iPSCs after genome editing of the sickle point mutation. Stem Cells. 2015;33:1470–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Patsali P, Turchiano G, Papasavva P, Romito M, Loucari CC, Stephanou C, et al. Correction of IVS I-110(G>A) beta-thalassemia by CRISPR/Cas-and TALEN-mediated disruption of aberrant regulatory elements in human hematopoietic stem and progenitor cells. Haematologica. 2019;104:e497–501.

    PubMed  PubMed Central  Google Scholar 

  88. Liang P, Ding C, Sun H, Xie X, Xu Y, Zhang X, et al. Correction of beta-thalassemia mutant by base editor in human embryos. Protein Cell. 2017;8:811–22.

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by funding from the University of Health Sciences Lahore.

Author information

Author notes

  1. These authors contributed equally: Gibran Ali, Muhammad Akram Tariq

Authors and Affiliations

  1. Institute of Regenerative Medicine, Physiology and Cell Biology Department, University of Health Sciences Lahore, Khyaban-e-Jamia Punjab, Lahore, 54600, Pakistan

    Gibran Ali, Muhammad Akram Tariq & Fridoon Jawad Ahmad

  2. Department of Oncology Medicine, University of Texas Health Science Center at Tyler, 11937 US HWY 271, Tyler, 75708, TX, USA

    Kamran Shahid

  3. University of Health Sciences Lahore, Khyaban-e-Jamia Punjab, Lahore, 54600, Pakistan

    Javed Akram

Authors
  1. Gibran Ali
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Muhammad Akram Tariq
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kamran Shahid
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fridoon Jawad Ahmad
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Javed Akram
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Gibran Ali or Fridoon Jawad Ahmad.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ali, G., Tariq, M.A., Shahid, K. et al. Advances in genome editing: the technology of choice for precise and efficient β-thalassemia treatment. Gene Ther 28, 6–15 (2021). https://doi.org/10.1038/s41434-020-0153-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41434-020-0153-9

Search

Advanced search

Quick links