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Annual Review of Genomics and Human Genetics

Volume 24, 2023

Sickle Cell Disease: From Genetics to Curative Approaches

Abstract

Sickle cell disease (SCD) is a monogenic blood disease caused by a point mutation in the gene coding for β-globin. The abnormal hemoglobin [sickle hemoglobin (HbS)] polymerizes under low-oxygen conditions and causes red blood cells to sickle. The clinical presentation varies from very severe (with acute pain, chronic pain, and early mortality) to normal (few complications and a normal life span). The variability of SCD might be due (in part) to various genetic modulators. First, we review the main genetic factors, polymorphisms, and modifier genes that influence the expression of globin or otherwise modulate the severity of SCD. Considering SCD as a complex, multifactorial disorder is important for the development of appropriate pharmacological and genetic treatments. Second, we review the characteristics, advantages, and disadvantages of the latest advances in gene therapy for SCD, from lentiviral-vector-based approaches to gene-editing strategies.

Keyword(s): gene editing, gene therapy trials, genetic modifiers, genotoxicity, sickle cell disease, viral vectors
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/content/journals/10.1146/annurev-genom-120122-081037
2023-08-25
2024-04-28
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Literature Cited

  1. 1.
    Adeyemo TA, Ojewunmi OO, Oyetunji IA, Kalejaiye OO, Menzel S 2021. Fetal-haemoglobin enhancing genotype at BCL11A reduces HbA2 levels in patients with sickle cell anaemia. EJHaem 2:459–61
     [Google Scholar]
  2. 2.
    Akinsheye I, Alsultan A, Solovieff N, Ngo D, Baldwin CT et al. 2011. Fetal hemoglobin in sickle cell anemia. Blood 118:19–27
     [Google Scholar]
  3. 3.
    Amendola M, Brusson M, Miccio A. 2022. CRISPRthripsis: the risk of CRISPR/Cas9-induced chromothripsis in gene therapy. Stem Cells Transl. Med. 11:1003–9
     [Google Scholar]
  4. 4.
    Antonarakis SE, Boehm CD, Serjeant GR, Theisen CE, Dover GJ, Kazazian HH. 1984. Origin of the beta S-globin gene in blacks: the contribution of recurrent mutation or gene conversion or both. PNAS 81:853–56
     [Google Scholar]
  5. 5.
    Antoniou P, Hardouin G, Martinucci P, Frati G, Felix T et al. 2022. Base-editing-mediated dissection of a γ-globin cis-regulatory element for the therapeutic reactivation of fetal hemoglobin expression. Nat. Commun. 13:6618
     [Google Scholar]
  6. 6.
    Antoniou P, Miccio A, Brusson M. 2021. Base and prime editing technologies for blood disorders. Front. Genome Ed. 3:618406
     [Google Scholar]
  7. 7.
    Anzalone AV, Randolph PB, Davis JR, Sousa AA, Koblan LW et al. 2019. Search-and-replace genome editing without double-strand breaks or donor DNA. Nature 576:149–57
     [Google Scholar]
  8. 8.
    Ashley-Koch AE, Elliott L, Kail ME, De Castro LM, Jonassaint J et al. 2008. Identification of genetic polymorphisms associated with risk for pulmonary hypertension in sickle cell disease. Blood 111:5721–26
     [Google Scholar]
  9. 9.
    Aydin M, Dovern E, Leeflang MMG, de la Fuente J, Kassim AA et al. 2021. Haploidentical allogeneic stem cell transplantation in sickle cell disease: a systematic review and meta-analysis. Transplant. Cell. Ther. 27:1004.e1–8
     [Google Scholar]
  10. 10.
    Ballas SK, Talacki CA, Adachi K, Schwartz E, Surrey S, Rappaport E. 1991. The Xmn I site (−158, C→T) 5′ to the Gγ gene: correlation with the Senegalese haplotype and Gγ globin expression. Hemoglobin 15:393–405
     [Google Scholar]
  11. 11.
    Batista JVGF, Arcanjo GS, Batista THC, Sobreira MJ, Santana RM et al. 2021. Influence of UGT1A1 promoter polymorphism, α-thalassemia and βS haplotype in bilirubin levels and cholelithiasis in a large sickle cell anemia cohort. Ann. Hematol. 100:903–11
     [Google Scholar]
  12. 12.
    Beet EA. 1947. Sickle cell disease in Northern Rhodesia. East Afr. Med. J. 24:212–22
     [Google Scholar]
  13. 13.
    Blackwell RQ, Oemijati S, Pribadi W, Weng MI, Liu CS. 1970. Hemoglobin G Makassar: β6 Glu→Ala. Biochim. Biophys. Acta Protein Struct. 214:396–401
     [Google Scholar]
  14. 14.
    Boutin J, Cappellen D, Rosier J, Amintas S, Dabernat S et al. 2022. ON-target adverse events of CRISPR-Cas9 nuclease: more chaotic than expected. CRISPR J 5:19–30
     [Google Scholar]
  15. 15.
    Brown CB, Boyer AS, Runyan RB, Barnett JV. 1999. Requirement of type III TGF-β receptor for endocardial cell transformation in the heart. Science 283:2080–82
     [Google Scholar]
  16. 16.
    Brunson A, Keegan THM, Bang H, Mahajan A, Paulukonis S, Wun T. 2017. Increased risk of leukemia among sickle cell disease patients in California. Blood 130:1597–99
     [Google Scholar]
  17. 17.
    Bungert J, Davé U, Lim KC, Lieuw KH, Shavit JA et al. 1995. Synergistic regulation of human β-globin gene switching by locus control region elements HS3 and HS4. Genes Dev 9:3083–96
     [Google Scholar]
  18. 18.
    Cappelli B, Volt F, Tozatto-Maio K, Scigliuolo GM, Ferster A et al. 2019. Risk factors and outcomes according to age at transplantation with an HLA-identical sibling for sickle cell disease. Haematologica 104:e543–46
     [Google Scholar]
  19. 19.
    Cent. Dis. Control Prev 2000. Update: newborn screening for sickle cell disease—California, Illinois, and New York, 1998. JAMA 284:1373–74
     [Google Scholar]
  20. 20.
    Charache S. 1990. Fetal hemoglobin, sickling, and sickle cell disease. Adv. Pediatr. 37:1–31
     [Google Scholar]
  21. 21.
    Charache S, Terrin ML, Moore RD, Dover GJ, Barton FB et al. 1995. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. N. Engl. J. Med. 332:1317–22
     [Google Scholar]
  22. 22.
    Coquerelle S, Ghardallou M, Rais S, Taupin P, Touzot F et al. 2019. Innovative curative treatment of beta thalassemia: cost-efficacy analysis of gene therapy versus allogenic hematopoietic stem-cell transplantation. Hum. Gene Ther 30:753–61
     [Google Scholar]
  23. 23.
    Cromer MK, Vaidyanathan S, Ryan DE, Curry B, Lucas AB et al. 2018. Global transcriptional response to CRISPR/Cas9-AAV6-based genome editing in CD34+ hematopoietic stem and progenitor cells. Mol. Ther. J. Am. Soc. Gene Ther. 26:2431–42
     [Google Scholar]
  24. 24.
    De Rijck J, de Kogel C, Demeulemeester J, Vets S, El Ashkar S et al. 2013. The BET family of proteins targets Moloney murine leukemia virus integration near transcription start sites. Cell Rep 5:886–94
     [Google Scholar]
  25. 25.
    Dever DP, Bak RO, Reinisch A, Camarena J, Washington G et al. 2016. CRISPR/Cas9 β-globin gene targeting in human haematopoietic stem cells. Nature 539:384–89
     [Google Scholar]
  26. 26.
    DeWitt MA, Magis W, Bray NL, Wang T, Berman JR et al. 2016. Selection-free genome editing of the sickle mutation in human adult hematopoietic stem/progenitor cells. Sci. Transl. Med. 8:360ra134
     [Google Scholar]
  27. 27.
    Doman JL, Raguram A, Newby GA, Liu DR. 2020. Evaluation and minimization of Cas9-independent off-target DNA editing by cytosine base editors. Nat. Biotechnol. 38:620–28
     [Google Scholar]
  28. 28.
    Doudna JA. 2020. The promise and challenge of therapeutic genome editing. Nature 578:229–36
     [Google Scholar]
  29. 29.
    Eaton WA, Bunn HF. 2017. Treating sickle cell disease by targeting HbS polymerization. Blood 129:2719–26
     [Google Scholar]
  30. 30.
    el-Hazmi MA, Bahakim HM, Warsy AS. 1992. DNA polymorphism in the beta-globin gene cluster in Saudi Arabs: relation to severity of sickle cell anaemia. Acta Haematol 88:61–66
     [Google Scholar]
  31. 31.
    Elenga N, Loko G, Etienne-Julan M, Al-Okka R, Adel AM, Yassin MA. 2022. Real-world data on efficacy of L-glutamine in preventing sickle cell disease-related complications in pediatric and adult patients. Front. Med. 9:931925
     [Google Scholar]
  32. 32.
    Esoh K, Wonkam-Tingang E, Wonkam A. 2021. Sickle cell disease in sub-Saharan Africa: transferable strategies for prevention and care. Lancet Haematol 8:e744–55
     [Google Scholar]
  33. 33.
    Esrick EB, Lehmann LE, Biffi A, Achebe M, Brendel C et al. 2021. Post-transcriptional genetic silencing of BCL11A to treat sickle cell disease. N. Engl. J. Med. 384:205–15
     [Google Scholar]
  34. 34.
    Ferrari S, Jacob A, Cesana D, Laugel M, Beretta S et al. 2022. Choice of template delivery mitigates the genotoxic risk and adverse impact of editing in human hematopoietic stem cells. Cell Stem Cell 29:1428–44.e9
     [Google Scholar]
  35. 35.
    Frangoul H, Altshuler D, Cappellini MD, Chen Y-S, Domm J et al. 2021. CRISPR-Cas9 gene editing for sickle cell disease and β-thalassemia. N. Engl. J. Med. 384:252–60
     [Google Scholar]
  36. 36.
    Frati G, Miccio A 2021. Genome editing for β-hemoglobinopathies: advances and challenges. J. Clin. Med. 10:482
     [Google Scholar]
  37. 37.
    Gaudelli NM, Lam DK, Rees HA, Solá-Esteves NM, Barrera LA et al. 2020. Directed evolution of adenine base editors with increased activity and therapeutic application. Nat. Biotechnol. 38:892–900
     [Google Scholar]
  38. 38.
    Germino-Watnick P, Hinds M, Le A, Chu R, Liu X, Uchida N 2022. Hematopoietic stem cell gene-addition/editing therapy in sickle cell disease. Cells 11:1843
     [Google Scholar]
  39. 39.
    Goyal S, Tisdale J, Schmidt M, Kanter J, Jaroscak J et al. 2022. Acute myeloid leukemia case after gene therapy for sickle cell disease. N. Engl. J. Med. 386:138–47
     [Google Scholar]
  40. 40.
    Grimley M, Asnani M, Shrestha A, Felker S, Lutzko C et al. 2020. Early results from a phase 1/2 study of Aru-1801 gene therapy for sickle cell disease (SCD): manufacturing process enhancements improve efficacy of a modified gamma globin lentivirus vector and reduced intensity conditioning transplant. Blood 136:Suppl. 120–21
     [Google Scholar]
  41. 41.
    Grünewald J, Zhou R, Garcia SP, Iyer S, Lareau CA et al. 2019. Transcriptome-wide off-target RNA editing induced by CRISPR-guided DNA base editors. Nature 569:433–37
     [Google Scholar]
  42. 42.
    Gupta N, Mocumbi A, Arwal SH, Jain Y, Haileamlak AM et al. 2021. Prioritizing health-sector interventions for noncommunicable diseases and injuries in low- and lower-middle income countries: National NCDI Poverty Commissions. Glob. Health Sci. Pract. 9:626–39
     [Google Scholar]
  43. 43.
    Gutsaeva DR, Parkerson JB, Yerigenahally SD, Kurz JC, Schaub RG et al. 2011. Inhibition of cell adhesion by anti-P-selectin aptamer: a new potential therapeutic agent for sickle cell disease. Blood 117:727–35
     [Google Scholar]
  44. 44.
    Haapaniemi E, Botla S, Persson J, Schmierer B, Taipale J. 2018. CRISPR-Cas9 genome editing induces a p53-mediated DNA damage response. Nat. Med. 24:927–30
     [Google Scholar]
  45. 45.
    Habib O, Habib G, Hwang G-H, Bae S. 2022. Comprehensive analysis of prime editing outcomes in human embryonic stem cells. Nucleic Acids Res 50:1187–97
     [Google Scholar]
  46. 46.
    Ho PT, Murgo AJ. 1995. Hydroxyurea and sickle cell crisis. N. Engl. J. Med. 333:1008
     [Google Scholar]
  47. 47.
    Hood AM, Crosby LE, Stotesbury H, Kölbel M, Kirkham FJ. 2022. Considerations for selecting cognitive endpoints and psychological patient-reported outcomes for clinical trials in pediatric patients with sickle cell disease. Front. Neurol. 13:835823
     [Google Scholar]
  48. 48.
    Hsieh MM, Bonner M, Pierciey FJ, Uchida N, Rottman J et al. 2020. Myelodysplastic syndrome unrelated to lentiviral vector in a patient treated with gene therapy for sickle cell disease. Blood Adv 4:2058–63
     [Google Scholar]
  49. 49.
    Ihry RJ, Worringer KA, Salick MR, Frias E, Ho D et al. 2018. p53 inhibits CRISPR-Cas9 engineering in human pluripotent stem cells. Nat. Med. 24:939–46
     [Google Scholar]
  50. 50.
    Ingram VM. 1956. A specific chemical difference between the globins of normal human and sickle-cell anaemia haemoglobin. Nature 178:792–94
     [Google Scholar]
  51. 51.
    Jiang J, Best S, Menzel S, Silver N, Lai MI et al. 2006. cMYB is involved in the regulation of fetal hemoglobin production in adults. Blood 108:1077–83
     [Google Scholar]
  52. 52.
    Jin S, Zong Y, Gao Q, Zhu Z, Wang Y et al. 2019. Cytosine, but not adenine, base editors induce genome-wide off-target mutations in rice. Science 364:292–95
     [Google Scholar]
  53. 53.
    Kanter J, Walters MC, Krishnamurti L, Mapara MY, Kwiatkowski JL et al. 2022. Biologic and clinical efficacy of LentiGlobin for sickle cell disease. N. Engl. J. Med. 386:617–28
     [Google Scholar]
  54. 54.
    Kaufmann JO, Krapels IPC, Van Brussel BTJ, Zekveld-Vroon RC, Oosterwijk JC et al. 2014. After the introduction into the national newborn screening program: Who is receiving genetic counseling for hemoglobinopathies in the Netherlands?. Public Health Genom 17:16–22
     [Google Scholar]
  55. 55.
    Kavanagh PL, Fasipe TA, Wun T. 2022. Sickle cell disease: a review. JAMA 328:57–68
     [Google Scholar]
  56. 56.
    Kharbanda S, Smith AR, Hutchinson SK, McKenna DH, Ball JB et al. 2014. Unrelated donor allogeneic hematopoietic stem cell transplantation for patients with hemoglobinopathies using a reduced-intensity conditioning regimen and third-party mesenchymal stromal cells. Biol. Blood Marrow Transplant. 20:581–86
     [Google Scholar]
  57. 57.
    Kosicki M, Tomberg K, Bradley A. 2018. Repair of double-strand breaks induced by CRISPR-Cas9 leads to large deletions and complex rearrangements. Nat. Biotechnol. 36:765–71
     [Google Scholar]
  58. 58.
    Lagresle-Peyrou C, Lefrère F, Magrin E, Ribeil J-A, Romano O et al. 2018. Plerixafor enables safe, rapid, efficient mobilization of hematopoietic stem cells in sickle cell disease patients after exchange transfusion. Haematologica 103:778–86
     [Google Scholar]
  59. 59.
    Lang CW, Stark AP, Acharya K, Ross LF. 2009. Maternal knowledge and attitudes about newborn screening for sickle cell disease and cystic fibrosis. Am. J. Med. Genet. A 149A:2424–29
     [Google Scholar]
  60. 60.
    Lattanzi A, Camarena J, Lahiri P, Segal H, Srifa W et al. 2021. Development of β-globin gene correction in human hematopoietic stem cells as a potential durable treatment for sickle cell disease. Sci. Transl. Med. 13:eabf2444
     [Google Scholar]
  61. 61.
    Lawn RM, Fritsch EF, Parker RC, Blake G, Maniatis T. 1978. The isolation and characterization of linked δ- and β-globin genes from a cloned library of human DNA. Cell 15:1157–74
     [Google Scholar]
  62. 62.
    Lee HK, Smith HE, Liu C, Willi M, Hennighausen L. 2020. Cytosine base editor 4 but not adenine base editor generates off-target mutations in mouse embryos. Commun. Biol. 3:19
     [Google Scholar]
  63. 63.
    Leonard A, Tisdale J, Abraham A. 2020. Curative options for sickle cell disease: haploidentical stem cell transplantation or gene therapy?. Br. J. Haematol. 189:408–23
     [Google Scholar]
  64. 64.
    Liu N, Hargreaves VV, Zhu Q, Kurland JV, Hong J et al. 2018. Direct promoter repression by BCL11A controls the fetal to adult hemoglobin switch. Cell 173:430–42.e17
     [Google Scholar]
  65. 65.
    Lobitz S, Telfer P, Cela E, Allaf B, Angastiniotis M et al. 2018. Newborn screening for sickle cell disease in Europe: recommendations from a Pan-European Consensus Conference. Br. J. Haematol. 183:648–60
     [Google Scholar]
  66. 66.
    Magis W, DeWitt MA, Wyman SK, Vu JT, Heo S-J et al. 2022. High-level correction of the sickle mutation is amplified in vivo during erythroid differentiation. iScience 25:104374
     [Google Scholar]
  67. 67.
    Magrin E, Semeraro M, Hebert N, Joseph L, Magnani A et al. 2022. Long-term outcomes of lentiviral gene therapy for the β-hemoglobinopathies: the HGB-205 trial. Nat. Med. 28:81–88
     [Google Scholar]
  68. 68.
    Marotta CA, Forget BG, Cohne-Solal M, Wilson JT, Weissman SM. 1977. Human beta-globin messenger RNA. I. Nucleotide sequences derived from complementary RNA. J. Biol. Chem. 252:5019–31
     [Google Scholar]
  69. 69.
    Martyn GE, Wienert B, Yang L, Shah M, Norton LJ et al. 2018. Natural regulatory mutations elevate the fetal globin gene via disruption of BCL11A or ZBTB7A binding. Nat. Genet. 50:498–503
     [Google Scholar]
  70. 70.
    Mayuranathan T, Yen JS, Newby GA, Yao Y, Porter SN et al. 2020. Adenosine base editing of γ-globin promoters induces fetal hemoglobin and inhibit erythroid sickling. Blood 136:Suppl. 121–22
     [Google Scholar]
  71. 71.
    Menzel S, Thein SL. 2019. Genetic modifiers of fetal haemoglobin in sickle cell disease. Mol. Diagn. Ther. 23:235–44
     [Google Scholar]
  72. 72.
    Métais J-Y, Doerfler PA, Mayuranathan T, Bauer DE, Fowler SC et al. 2019. Genome editing of HBG1 and HBG2 to induce fetal hemoglobin. Blood Adv 3:3379–92
     [Google Scholar]
  73. 73.
    Miller BA, Salameh M, Ahmed M, Olivieri N, Antognetti G et al. 1987. Analysis of hemoglobin F production in Saudi Arabian families with sickle cell anemia. Blood 70:716–20
     [Google Scholar]
  74. 74.
    Mohamad AS, Hamzah R, Selvaratnam V, Yegapan S, Sathar J. 2018. Human hemoglobin G-Makassar variant masquerading as sickle cell anemia. Hematol. Rep. 10:7210
     [Google Scholar]
  75. 75.
    Nagel RL, Steinberg MH. 2001. Role of epistatic (modifier) genes in the modulation of the phenotypic diversity of sickle cell anemia. Pediatr. Pathol. Mol. Med. 20:123–36
     [Google Scholar]
  76. 76.
    Nambiar TS, Baudrier L, Billon P, Ciccia A. 2022. CRISPR-based genome editing through the lens of DNA repair. Mol. Cell 82:348–88
     [Google Scholar]
  77. 77.
    Neel JV, Kodani M, Brewer R, Anderson RC. 1949. The incidence of consanguineous matings in Japan, with remarks on the estimation of comparative gene frequencies and the expected rate of appearance of induced recessive mutations. Am. J. Hum. Genet. 1:156–78
     [Google Scholar]
  78. 78.
    Negre O, Eggimann A-V, Beuzard Y, Ribeil J-A, Bourget P et al. 2016. Gene therapy of the β-hemoglobinopathies by lentiviral transfer of the βA(T87Q)-globin gene. Hum. Gene Ther 27:148–65
     [Google Scholar]
  79. 79.
    Newby GA, Yen JS, Woodard KJ, Mayuranathan T, Lazzarotto CR et al. 2021. Base editing of haematopoietic stem cells rescues sickle cell disease in mice. Nature 595:295–302
     [Google Scholar]
  80. 80.
    Niihara Y, Miller ST, Kanter J, Lanzkron S, Smith WR et al. 2018. A phase 3 trial of l-glutamine in sickle cell disease. N. Engl. J. Med. 379:226–35
     [Google Scholar]
  81. 81.
    Nur E, Biemond BJ, Otten H-M, Brandjes DP, Schnog J-JB, Study Group CURAMA 2011. Oxidative stress in sickle cell disease; pathophysiology and potential implications for disease management. Am. J. Hematol. 86:484–89
     [Google Scholar]
  82. 82.
    Onwubalili JK. 1983. Sickle-cell anaemia: an explanation for the ancient myth of reincarnation in Nigeria. Lancet 322:503–5
     [Google Scholar]
  83. 83.
    Patel DA, Akinsete AM, de la Fuente J, Kassim AA. 2020. Haploidentical bone marrow transplant with posttransplant cyclophosphamide for sickle cell disease: an update. Hematol. Oncol. Stem Cell Ther. 13:91–97
     [Google Scholar]
  84. 84.
    Pauling L, Itano HA, Singer SJ, Wells IC. 1949. Sickle cell anemia, a molecular disease. Science 110:543–48
     [Google Scholar]
  85. 85.
    Piel FB, Hay SI, Gupta S, Weatherall DJ, Williams TN. 2013. Global burden of sickle cell anaemia in children under five, 2010–2050: modelling based on demographics, excess mortality, and interventions. PLOS Med 10:e1001484
     [Google Scholar]
  86. 86.
    Piel FB, Patil AP, Howes RE, Nyangiri OA, Gething PW et al. 2010. Global distribution of the sickle cell gene and geographical confirmation of the malaria hypothesis. Nat. Commun. 1:104
     [Google Scholar]
  87. 87.
    Porto EM, Komor AC, Slaymaker IM, Yeo GW. 2020. Base editing: advances and therapeutic opportunities. Nat. Rev. Drug Discov. 19:839–59
     [Google Scholar]
  88. 88.
    Raphael JL, Mei M, Mueller BU, Giordano T. 2012. High resource hospitalizations among children with vaso-occlusive crises in sickle cell disease. Pediatr. Blood Cancer 58:584–90
     [Google Scholar]
  89. 89.
    Ravi NS, Wienert B, Wyman SK, Bell HW, George A et al. 2022. Identification of novel HPFH-like mutations by CRISPR base editing that elevate the expression of fetal hemoglobin. eLife 11:e65421
     [Google Scholar]
  90. 90.
    Rees HA, Komor AC, Yeh W-H, Caetano-Lopes J, Warman M et al. 2017. Improving the DNA specificity and applicability of base editing through protein engineering and protein delivery. Nat. Commun. 8:15790
     [Google Scholar]
  91. 91.
    Ribeil J-A, Hacein-Bey-Abina S, Payen E, Magnani A, Semeraro M et al. 2017. Gene therapy in a patient with sickle cell disease. N. Engl. J. Med. 376:848–55
     [Google Scholar]
  92. 92.
    Rodgers GP. 1992. Spectrum of fetal hemoglobin responses in sickle cell patients treated with hydroxyurea: the National Institutes of Health experience. Semin. Oncol. 19:Suppl. 967–73
     [Google Scholar]
  93. 93.
    Rowley PT. 1989. Parental receptivity to neonatal sickle trait identification. Pediatrics 83:891–93
     [Google Scholar]
  94. 94.
    Rumaney MB, Ngo Bitoungui VJ, Vorster AA, Ramesar R, Kengne AP et al. 2014. The co-inheritance of alpha-thalassemia and sickle cell anemia is associated with better hematological indices and lower consultations rate in Cameroonian patients and could improve their survival. PLOS ONE 9:e100516
     [Google Scholar]
  95. 95.
    Savitt TL, Goldberg MF. 1989. Herrick's 1910 case report of sickle cell anemia: the rest of the story. JAMA 261:266–71
     [Google Scholar]
  96. 96.
    Schiroli G, Conti A, Ferrari S, Della Volpe L, Jacob A et al. 2019. Precise gene editing preserves hematopoietic stem cell function following transient p53-mediated DNA damage response. Cell Stem Cell 24:551–65.e8
     [Google Scholar]
  97. 97.
    Schultz WH, Ware RE. 2003. Malignancy in patients with sickle cell disease. Am. J. Hematol. 74:249–53
     [Google Scholar]
  98. 98.
    Steinberg MH. 2008. Sickle cell anemia, the first molecular disease: overview of molecular etiology, pathophysiology, and therapeutic approaches. ScientificWorldJournal 8:1295–324
     [Google Scholar]
  99. 99.
    Tanhehco YC. 2021. Gene therapy for hemoglobinopathies. Transfus. Apher. Sci. 60:103061
     [Google Scholar]
  100. 100.
    Tayyaba Rehan S, Hussain HU, Malik F, Usama RM, Tahir MJ, Asghar MS. 2022. Voxelotor versus other therapeutic options for sickle cell disease: Are we still lagging behind in treating the disease?. Health Sci. Rep. 5:e713
     [Google Scholar]
  101. 101.
    Tchernia G. 2004.. [ The long story of sickle cell disease. ]. Rev. Prat. 54:1618–21 ( In French )
     [Google Scholar]
  102. 102.
    Tchernia G, Bardakdjian J, Lainé A, Ly A, Orssaud G, Larnaudie S. 2008. [A center in Paris for screening and counselling sickle cell patients and carriers]. Bull. Acad. Natl. Med. 192:1349–59 ( In French )
     [Google Scholar]
  103. 103.
    Thielen FW, Houwing ME, Cnossen MH, Al Hadithy-Irgiztseva IA, Hazelzet JA et al. 2020. Cost of health care for paediatric patients with sickle cell disease: an analysis of resource use and costs in a European country. Pediatr. Blood Cancer 67:e28588
     [Google Scholar]
  104. 104.
    Thompson AA, Walters MC, Kwiatkowski J, Rasko JEJ, Ribeil J-A et al. 2018. Gene therapy in patients with transfusion-dependent β-thalassemia. N. Engl. J. Med. 378:1479–93
     [Google Scholar]
  105. 105.
    Tolhuis B, Palstra RJ, Splinter E, Grosveld F, de Laat W. 2002. Looping and interaction between hypersensitive sites in the active β-globin locus. Mol. Cell 10:1453–65
     [Google Scholar]
  106. 106.
    Traxler EA, Yao Y, Wang Y-D, Woodard KJ, Kurita R et al. 2016. A genome-editing strategy to treat β-hemoglobinopathies that recapitulates a mutation associated with a benign genetic condition. Nat. Med. 22:987–90
     [Google Scholar]
  107. 107.
    Treadwell MJ, Mushiana S, Badawy SM, Preiss L, King AA et al. 2022. An evaluation of patient-reported outcomes in sickle cell disease within a conceptual model. Qual. Life Res. 31:2681–94
     [Google Scholar]
  108. 108.
    Tu T, Song Z, Liu X, Wang S, He X et al. 2022. A precise and efficient adenine base editor. Mol. Ther. 30:2933–41
     [Google Scholar]
  109. 109.
    Uyoga S, Macharia AW, Mochamah G, Ndila CM, Nyutu G et al. 2019. The epidemiology of sickle cell disease in children recruited in infancy in Kilifi, Kenya: a prospective cohort study. Lancet Glob. Health 7:e1458–66
     [Google Scholar]
  110. 110.
    Vakulskas CA, Dever DP, Rettig GR, Turk R, Jacobi AM et al. 2018. A high-fidelity Cas9 mutant delivered as a ribonucleoprotein complex enables efficient gene editing in human hematopoietic stem and progenitor cells. Nat. Med. 24:1216–24
     [Google Scholar]
  111. 111.
    Vasavda N, Menzel S, Kondaveeti S, Maytham E, Awogbade M et al. 2007. The linear effects of α-thalassaemia, the UGT1A1 and HMOX1 polymorphisms on cholelithiasis in sickle cell disease. Br. J. Haematol. 138:263–70
     [Google Scholar]
  112. 112.
    Vichinsky E, Hoppe CC, Ataga KI, Ware RE, Nduba V et al. 2019. A phase 3 randomized trial of voxelotor in sickle cell disease. N. Engl. J. Med. 381:509–19
     [Google Scholar]
  113. 113.
    Vichinsky E, Hurst D, Earles A, Kleman K, Lubin B. 1988. Newborn screening for sickle cell disease: effect on mortality. Pediatrics 81:749–55
     [Google Scholar]
  114. 114.
    Viprakasit V, Wiriyasateinkul A, Sattayasevana B, Miles KL, Laosombat V. 2002. Hb G-Makassar [β6(A3)Glu→Ala; codon 6 (G A G→G C G)]: molecular characterization, clinical, and hematological effects. Hemoglobin 26:245–53
     [Google Scholar]
  115. 115.
    Walters MC, De Castro LM, Sullivan KM, Krishnamurti L, Kamani N et al. 2016. Indications and results of HLA-identical sibling hematopoietic cell transplantation for sickle cell disease. Biol. Blood Marrow Transplant. 22:207–11
     [Google Scholar]
  116. 116.
    Ware RE, de Montalembert M, Tshilolo L, Abboud MR 2017. Sickle cell disease. Lancet 390:311–23
     [Google Scholar]
  117. 117.
    Weatherall D, Hofman K, Rodgers G, Ruffin J, Hrynkow S. 2005. A case for developing North-South partnerships for research in sickle cell disease. Blood 105:921–23
     [Google Scholar]
  118. 118.
    Weber L, Frati G, Felix T, Hardouin G, Casini A et al. 2020. Editing a γ-globin repressor binding site restores fetal hemoglobin synthesis and corrects the sickle cell disease phenotype. Sci. Adv. 6:eaay9392
     [Google Scholar]
  119. 119.
    Wonkam A, Ngo Bitoungui VJ, Vorster AA, Ramesar R, Cooper RS et al. 2014. Association of variants at BCL11A and HBS1L-MYB with hemoglobin F and hospitalization rates among sickle cell patients in Cameroon. PLOS ONE 9:e92506
     [Google Scholar]
  120. 120.
    Yang YM, Pace B. 2001. Pharmacologic induction of fetal hemoglobin synthesis: cellular and molecular mechanisms. Pediatr. Pathol. Mol. Med. 20:87–106
     [Google Scholar]
  121. 121.
    Zeng J, Wu Y, Ren C, Bonanno J, Shen AH et al. 2020. Therapeutic base editing of human hematopoietic stem cells. Nat. Med. 26:535–41
     [Google Scholar]
  122. 122.
    Zhou C, Sun Y, Yan R, Liu Y, Zuo E et al. 2019. Off-target RNA mutation induced by DNA base editing and its elimination by mutagenesis. Nature 571:275–78
     [Google Scholar]
  123. 123.
    Zuo E, Sun Y, Wei W, Yuan T, Ying W et al. 2019. Cytosine base editor generates substantial off-target single-nucleotide variants in mouse embryos. Science 364:289–92
     [Google Scholar]
  124. 124.
    Zuo E, Sun Y, Yuan T, He B, Zhou C et al. 2020. A rationally engineered cytosine base editor retains high on-target activity while reducing both DNA and RNA off-target effects. Nat. Methods 17:600–4
     [Google Scholar]
/content/journals/10.1146/annurev-genom-120122-081037
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Sickle Cell Disease: From Genetics to Curative Approaches
Annual Review of Genomics and Human Genetics 24, 255 (2023); https://doi.org/10.1146/annurev-genom-120122-081037
/content/journals/10.1146/annurev-genom-120122-081037
/content/journals/10.1146/annurev-genom-120122-081037
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