Nucleic Acid Therapy for β-Thalassemia

Overview

Journal Biologics

Date 2020 Sep 28

PMID 32982166

Citations 5

Authors

Annette dArqom

Affiliations

Soon will be listed here.

Abstract

β-thalassemia is caused by mutations in the β-globin gene which diminishes or abolishes β-globin chain production. This reduction causes an imbalance of the α/β-globin chain ratio and contributes to the pathogenesis of the disease. Several approaches to reduce the imbalance of the α/β ratio using several nucleic acid-based technologies such as RNAi, lentiviral mediated gene therapy, splice switching oligonucleotides (SSOs) and gene editing technology have been investigated extensively. These approaches aim to reduce excess free α-globin, either by reducing the α-globin chain, restoring β-globin expression and reactivating γ-globin expression, leading a reduced disease severity, treatment necessity, treatment interval, and disease complications, thus, increasing the life quality of the patients and alleviating economic burden. Therefore, nucleic acid-based therapy might become a potential targeted therapy for β-thalassemia.

Citing Articles

Potential Use of MicroRNA Technology in Thalassemia Therapy.

Rujito L, Wardana T, Siswandari W, Nainggolan I, Sasongko T J Clin Med Res. 2024; 16(9):411-422.

PMID: 39346566 PMC: 11426174. DOI: 10.14740/jocmr5245.

Role of Hemin in the Immune Response of T Follicular Helper Lymphocytes Expressing T-Cell Immunoreceptor with Immunoglobulin and Immunoreceptor Tyrosine-Based Inhibitory Domains, Programmed Cell Death-1, and Interleukin-21 in Allo-Auto Positive and....

Tambunan B, Ugrasena I, Aryati J Blood Med. 2023; 14:7-17.

PMID: 36660451 PMC: 9844107. DOI: 10.2147/JBM.S393134.

Impact of Hemin on Interleukin-21 Levels and Plasma Cells in Transfusion-Dependent Thalassemia with Positive and Negative Allo-Autoantibody.

Tambunan B, Ugrasena I, Aryati A Int J Gen Med. 2023; 16:47-56.

PMID: 36636711 PMC: 9830417. DOI: 10.2147/IJGM.S397317.

Molecular genetics of β-thalassemia: A narrative review.

Jaing T, Chang T, Chen S, Lin C, Wen Y, Chiu C Medicine (Baltimore). 2021; 100(45):e27522.

PMID: 34766559 PMC: 8589257. DOI: 10.1097/MD.0000000000027522.

Attitudes of Indonesian Medical Doctors and Medical Students Toward Genome Editing.

Izzah S, Setyanto D, Hasanatuludhhiyah N, Indiastuti D, Nasution Z, dArqom A J Multidiscip Healthc. 2021; 14:1017-1027.

PMID: 33981145 PMC: 8106925. DOI: 10.2147/JMDH.S303881.

References

Guda S, Brendel C, Renella R, Du P, Bauer D, Canver M . miRNA-embedded shRNAs for Lineage-specific BCL11A Knockdown and Hemoglobin F Induction. Mol Ther. 2015; 23(9):1465-74. PMC: 4817887. DOI: 10.1038/mt.2015.113. View

Antony J, Latifi N, Haque A, Lamsfus-Calle A, Daniel-Moreno A, Graeter S . Gene correction of HBB mutations in CD34 hematopoietic stem cells using Cas9 mRNA and ssODN donors. Mol Cell Pediatr. 2018; 5(1):9. PMC: 6236008. DOI: 10.1186/s40348-018-0086-1. View

Miccio A, Cesari R, Lotti F, Rossi C, Sanvito F, Ponzoni M . In vivo selection of genetically modified erythroblastic progenitors leads to long-term correction of beta-thalassemia. Proc Natl Acad Sci U S A. 2008; 105(30):10547-52. PMC: 2492493. DOI: 10.1073/pnas.0711666105. View

Rinaldi C, Wood M . Antisense oligonucleotides: the next frontier for treatment of neurological disorders. Nat Rev Neurol. 2017; 14(1):9-21. DOI: 10.1038/nrneurol.2017.148. View

Mansoori Derakhshan S, Shekari Khaniani M . Restoration of correct splicing in IVSI-110 mutation of β-globin gene with antisense oligonucleotides: implications and applications in functional assay development. Iran J Basic Med Sci. 2017; 20(6):700-707. PMC: 5569442. DOI: 10.22038/IJBMS.2017.8840. View

Crooke S, Vickers T, Liang X . Phosphorothioate modified oligonucleotide-protein interactions. Nucleic Acids Res. 2020; 48(10):5235-5253. PMC: 7261153. DOI: 10.1093/nar/gkaa299. View

Carroll D . Genome engineering with zinc-finger nucleases. Genetics. 2011; 188(4):773-82. PMC: 3176093. DOI: 10.1534/genetics.111.131433. View

Rivella S . Ineffective erythropoiesis and thalassemias. Curr Opin Hematol. 2009; 16(3):187-94. PMC: 3703923. DOI: 10.1097/MOH.0b013e32832990a4. View

Madocsai C, Lim S, Geib T, Lam B, Hertel K . Correction of SMN2 Pre-mRNA splicing by antisense U7 small nuclear RNAs. Mol Ther. 2005; 12(6):1013-22. DOI: 10.1016/j.ymthe.2005.08.022. View

10.

Hammond S, Wood M . Genetic therapies for RNA mis-splicing diseases. Trends Genet. 2011; 27(5):196-205. DOI: 10.1016/j.tig.2011.02.004. View

11.

Suwanmanee T, Sierakowska H, Lacerra G, Svasti S, Kirby S, Walsh C . Restoration of human beta-globin gene expression in murine and human IVS2-654 thalassemic erythroid cells by free uptake of antisense oligonucleotides. Mol Pharmacol. 2002; 62(3):545-53. DOI: 10.1124/mol.62.3.545. View

12.

Kouranova E, Forbes K, Zhao G, Warren J, Bartels A, Wu Y . CRISPRs for Optimal Targeting: Delivery of CRISPR Components as DNA, RNA, and Protein into Cultured Cells and Single-Cell Embryos. Hum Gene Ther. 2016; 27(6):464-75. PMC: 4931306. DOI: 10.1089/hum.2016.009. View

13.

Bolotin A, Quinquis B, Sorokin A, Ehrlich S . Clustered regularly interspaced short palindrome repeats (CRISPRs) have spacers of extrachromosomal origin. Microbiology (Reading). 2005; 151(Pt 8):2551-2561. DOI: 10.1099/mic.0.28048-0. View

14.

Goyenvalle A, Wright J, Babbs A, Wilkins V, Garcia L, Davies K . Engineering multiple U7snRNA constructs to induce single and multiexon-skipping for Duchenne muscular dystrophy. Mol Ther. 2012; 20(6):1212-21. PMC: 3369406. DOI: 10.1038/mt.2012.26. View

15.

Schmajuk G, Sierakowska H, Kole R . Antisense oligonucleotides with different backbones. Modification of splicing pathways and efficacy of uptake. J Biol Chem. 1999; 274(31):21783-9. DOI: 10.1074/jbc.274.31.21783. View

16.

Yang F, Liu C, Chen D, Tu M, Xie H, Sun H . CRISPR/Cas9-loxP-Mediated Gene Editing as a Novel Site-Specific Genetic Manipulation Tool. Mol Ther Nucleic Acids. 2017; 7:378-386. PMC: 5429228. DOI: 10.1016/j.omtn.2017.04.018. View

17.

Li G, Zhang X, Zhong C, Mo J, Quan R, Yang J . Small molecules enhance CRISPR/Cas9-mediated homology-directed genome editing in primary cells. Sci Rep. 2017; 7(1):8943. PMC: 5566437. DOI: 10.1038/s41598-017-09306-x. View

18.

Thein S . Molecular basis of β thalassemia and potential therapeutic targets. Blood Cells Mol Dis. 2017; 70:54-65. PMC: 5738298. DOI: 10.1016/j.bcmd.2017.06.001. View

19.

Gorman L, Suter D, Emerick V, Schumperli D, Kole R . Stable alteration of pre-mRNA splicing patterns by modified U7 small nuclear RNAs. Proc Natl Acad Sci U S A. 1998; 95(9):4929-34. PMC: 20190. DOI: 10.1073/pnas.95.9.4929. View

20.

Shariati L, Khanahmad H, Salehi M, Hejazi Z, Rahimmanesh I, Tabatabaiefar M . Genetic disruption of the KLF1 gene to overexpress the γ-globin gene using the CRISPR/Cas9 system. J Gene Med. 2016; 18(10):294-301. DOI: 10.1002/jgm.2928. View