Science Reviews - Biology, 2023, 2(3), 18 - 24 Martina Rossi
Advancements and Challenges in Gene Therapy Ap-
proaches for Sickle Cell Disease: A Comprehensive
Martina Rossi, PhD
Independent Researcher, Strasbourg, France;
1. Kuriri FA. Hope on the Horizon: New and Future Therapies for Sickle Cell Disease. J Clin Med. 2023
Sep 1;12(17):5692.
2. Lattanzi A, Camarena J, Lahiri P, Segal H, Srifa W, Vakulskas CA, et al. Development of β-globin
gene correction in human hematopoietic stem cells as a potential durable treatment for sickle cell dis-
ease. Sci Transl Med. 2021 Jun 16;13(598):eabf2444.
3. Hardouin G, Magrin E, Corsia A, Cavazzana M, Miccio A, Semeraro M. Sickle Cell Disease: From
Genetics to Curative Approaches. Annu Rev Genomics Hum Genet. 2023 Aug 25;24:25575.
4. National Academies of Sciences E, Division H and M, Practice B on PH and PH, Action C on
ASCDASP and B for, Martinez RM, Osei-Anto HA, et al. Complications of Sickle Cell Disease and
Current Management Approaches. In: Addressing Sickle Cell Disease: A Strategic Plan and Blueprint
for Action [Internet]. National Academies Press (US); 2020
5. Esoh K, Wonkam A. Evolutionary history of sickle-cell mutation: implications for global genetic med-
icine. Hum Mol Genet. 2021 Apr 26;30(R1):R11928.
6. Depetris-Chauvin E, Weil DN. Malaria and Early African Development: Evidence from the Sickle Cell
Trait. Econ J (London). 2018 May;128(610):120734.
7. Eridani S. Sickle cell protection from malaria. Hematol Rep. 2011 Nov 4;3(3):e24.
8. Sedrak A, Kondamudi NP. Sickle Cell Disease. In: StatPearls. Treasure Island (FL): StatPearls Publish-
ing; 2023.
9. Howard J. Sickle cell disease: when and how to transfuse. Hematology Am Soc Hematol Educ Pro-
gram. 2016 Dec 2;2016(1):62531.
10. Agrawal RK, Patel RK, Shah V, Nainiwal L, Trivedi B. Hydroxyurea in Sickle Cell Disease: Drug Re-
view. Indian J Hematol Blood Transfus. 2014 Jun;30(2):916. 1.
11. Germino-Watnick P, Hinds M, Le A, Chu R, Liu X, Uchida N. Hematopoietic Stem Cell Gene-
Addition/Editing Therapy in Sickle Cell Disease. Cells. 2022 Jan;11(11):1843.
12. Ashorobi D, Naha K, Bhatt R. Hematopoietic Stem Cell Transplantation in Sickle Cell Disease. In:
StatPearls. Treasure Island (FL): StatPearls Publishing; 2023.
13. Cavazzana M, Antoniani C, Miccio A. Gene Therapy for β-Hemoglobinopathies. Mol Ther. 2017 May
14. White SL, Hart K, Kohn DB. Diverse Approaches to Gene Therapy of Sickle Cell Disease. Annu Rev
Med. 2023 Jan 27;74:47387.
Martina Rossi Science Reviews - Biology, 2023, 2(3), 18 - 24
15. Dong W, Kantor B. Lentiviral Vectors for Delivery of Gene-Editing Systems Based on CRISPR/Cas:
Current State and Perspectives. Viruses. 2021 Jul 1;13(7):1288.
16. May C, Rivella S, Callegari J, Heller G, Gaensler KM, Luzzatto L, et al. Therapeutic haemoglobin
synthesis in beta-thalassaemic mice expressing lentivirus-encoded human beta-globin. Nature. 2000
Jul 6;406(6791):826.
17. Magrin E, Miccio A, Cavazzana M. Lentiviral and genome-editing strategies for the treatment of β-
hemoglobinopathies. Blood. 2019 Oct 10;134(15):120313.
18. Brendel, C., Guda, S., Renella, R., Bauer, D.E., Canver, M.C., Kim, Y.-J., Heeney, M.M., Klatt, D., Fogel,
J., Milsom, M.D., et al. (2016). Lineage-specific BCL11A knockdown circumvents toxicities and re-
verses sickle phenotype. J. Clin. Invest. 126, 38683878.
19. Guda, S., Brendel, C., Renella, R., Du, P., Bauer, D.E., Canver, M.C., Grenier, J.K., Grimson, A.W.,
Kamran, S.C., Thornton, J., et al. (2015). miRNA-embedded shRNAs for lineage-specific BCL11A
knockdown and hemoglobin F induction. Mol. Ther. 23, 14651474.
20. Brendel, C., Negre, O., Rothe, M., Guda, S., Parsons, G., Harris, C., McGuinness, M., Abriss, D.,
Tsytsykova, A., Klatt, D., et al. (2020). Preclinical evaluation of a novel len- tiviral vector driving line-
age-specific BCL11A knockdown for sickle cell gene therapy. Mol. Ther. Methods Clin. Dev. 17, 589
600. 03.015.
21. Brusson M, Chalumeau A, Martinucci P, Romano O, Felix T, Poletti V, et al. Novel lentiviral vectors
for gene therapy of sickle cell disease combining gene addition and gene silencing strategies. Mol
Ther Nucleic Acids. 2023 Jun 13;32:22946.
22. Cornu T, Mussolino C, Cathomen T. Refining strategies to translate genome editing to the clinic. Nat
Med. (2017) 23:41523.
23. Carusillo A, Mussolino C. DNA damage: from threat to treatment. Cells. (2020) 9:1665.
24. Salisbury-Ruf C, Larochelle A. Advances and obstacles in homology- mediated gene editing of hema-
topoietic stem cells. J Clin Med. (2021) 10:513.
25. Cannan WJ, Pederson DS. Mechanisms and Consequences of Double-strand DNA Break Formation in
Chromatin. J Cell Physiol. 2016 Jan;231(1):314.
26. Ran F, Hsu P, Lin C, Gootenberg J, Konermann S, Trevino A, et al. Double nicking by RNA-guided
CRISPR Cas9 for enhanced genome editing specificity. Cell. (2013) 154:13809.
27. Newby GA, Yen JS, Woodard KJ, Mayuranathan T, Lazzarotto CR, Li Y, et al. Base editing of haema-
topoietic stem cells rescues sickle cell disease in mice. Nature. 2021 Jul;595(7866):295302.
28. Everette KA, Newby GA, Levine RM, Mayberry K, Jang Y, Mayuranathan T, et al. Ex vivo prime edit-
ing of patient haematopoietic stem cells rescues sickle-cell disease phenotypes after engraftment in
mice. Nat Biomed Eng. 2023 May;7(5):61628.
Conflict of Interest statement
The author declares no conflict of interest.