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Genetic Manipulation Strategies for β-Thalassemia: A Review
Thalassemias are monogenic hematologic diseases that are classified as α- or β-thalassemia according to its quantitative abnormalities of adult α- or β-globin chains. β-thalassemia has widely spread throughout the world especially in Mediterranean countries, the Middle East, Central Asia, India, Sou...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9240386/ https://www.ncbi.nlm.nih.gov/pubmed/35783328 http://dx.doi.org/10.3389/fped.2022.901605 |
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author | Zakaria, Nur Atikah Bahar, Rosnah Abdullah, Wan Zaidah Mohamed Yusoff, Abdul Aziz Shamsuddin, Shaharum Abdul Wahab, Ridhwan Johan, Muhammad Farid |
author_facet | Zakaria, Nur Atikah Bahar, Rosnah Abdullah, Wan Zaidah Mohamed Yusoff, Abdul Aziz Shamsuddin, Shaharum Abdul Wahab, Ridhwan Johan, Muhammad Farid |
author_sort | Zakaria, Nur Atikah |
collection | PubMed |
description | Thalassemias are monogenic hematologic diseases that are classified as α- or β-thalassemia according to its quantitative abnormalities of adult α- or β-globin chains. β-thalassemia has widely spread throughout the world especially in Mediterranean countries, the Middle East, Central Asia, India, Southern China, and the Far East as well as countries along the north coast of Africa and in South America. The one and the only cure for β-thalassemia is allogenic hematopoietic stem cell transplantations (HSCT). Nevertheless, the difficulty to find matched donors has hindered the availability of this therapeutic option. Therefore, this present review explored the alternatives for β-thalassemia treatment such as RNA manipulation therapy, splice-switching, genome editing and generation of corrected induced pluripotent stem cells (iPSCs). Manipulation of β-globin RNA is mediated by antisense oligonucleotides (ASOs) or splice-switching oligonucleotides (SSOs), which redirect pre-mRNA splicing to significantly restore correct β-globin pre-mRNA splicing and gene product in cultured erythropoietic cells. Zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) are designer proteins that can alter the genome precisely by creating specific DNA double-strand breaks. The treatment of β-thalassemia patient-derived iPSCs with TALENs have been found to correct the β-globin gene mutations, implying that TALENs could be used as a therapy option for β-thalassemia. Additionally, CRISPR technologies using Cas9 have been used to fix mutations in the β-globin gene in cultured cells as well as induction of hereditary persistence of fetal hemoglobin (HPFH), and α-globin gene deletions have proposed a possible therapeutic option for β-thalassemia. Overall, the accumulated research evidence demonstrated the potential of ASOs-mediated aberrant splicing correction of β-thalassemia mutations and the advancements of genome therapy approaches using ZFNs, TALENs, and CRISPR/Cas9 that provided insights in finding the permanent cure of β-thalassemia. |
format | Online Article Text |
id | pubmed-9240386 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92403862022-06-30 Genetic Manipulation Strategies for β-Thalassemia: A Review Zakaria, Nur Atikah Bahar, Rosnah Abdullah, Wan Zaidah Mohamed Yusoff, Abdul Aziz Shamsuddin, Shaharum Abdul Wahab, Ridhwan Johan, Muhammad Farid Front Pediatr Pediatrics Thalassemias are monogenic hematologic diseases that are classified as α- or β-thalassemia according to its quantitative abnormalities of adult α- or β-globin chains. β-thalassemia has widely spread throughout the world especially in Mediterranean countries, the Middle East, Central Asia, India, Southern China, and the Far East as well as countries along the north coast of Africa and in South America. The one and the only cure for β-thalassemia is allogenic hematopoietic stem cell transplantations (HSCT). Nevertheless, the difficulty to find matched donors has hindered the availability of this therapeutic option. Therefore, this present review explored the alternatives for β-thalassemia treatment such as RNA manipulation therapy, splice-switching, genome editing and generation of corrected induced pluripotent stem cells (iPSCs). Manipulation of β-globin RNA is mediated by antisense oligonucleotides (ASOs) or splice-switching oligonucleotides (SSOs), which redirect pre-mRNA splicing to significantly restore correct β-globin pre-mRNA splicing and gene product in cultured erythropoietic cells. Zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) are designer proteins that can alter the genome precisely by creating specific DNA double-strand breaks. The treatment of β-thalassemia patient-derived iPSCs with TALENs have been found to correct the β-globin gene mutations, implying that TALENs could be used as a therapy option for β-thalassemia. Additionally, CRISPR technologies using Cas9 have been used to fix mutations in the β-globin gene in cultured cells as well as induction of hereditary persistence of fetal hemoglobin (HPFH), and α-globin gene deletions have proposed a possible therapeutic option for β-thalassemia. Overall, the accumulated research evidence demonstrated the potential of ASOs-mediated aberrant splicing correction of β-thalassemia mutations and the advancements of genome therapy approaches using ZFNs, TALENs, and CRISPR/Cas9 that provided insights in finding the permanent cure of β-thalassemia. Frontiers Media S.A. 2022-06-15 /pmc/articles/PMC9240386/ /pubmed/35783328 http://dx.doi.org/10.3389/fped.2022.901605 Text en Copyright © 2022 Zakaria, Bahar, Abdullah, Mohamed Yusoff, Shamsuddin, Abdul Wahab and Johan. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pediatrics Zakaria, Nur Atikah Bahar, Rosnah Abdullah, Wan Zaidah Mohamed Yusoff, Abdul Aziz Shamsuddin, Shaharum Abdul Wahab, Ridhwan Johan, Muhammad Farid Genetic Manipulation Strategies for β-Thalassemia: A Review |
title | Genetic Manipulation Strategies for β-Thalassemia: A Review |
title_full | Genetic Manipulation Strategies for β-Thalassemia: A Review |
title_fullStr | Genetic Manipulation Strategies for β-Thalassemia: A Review |
title_full_unstemmed | Genetic Manipulation Strategies for β-Thalassemia: A Review |
title_short | Genetic Manipulation Strategies for β-Thalassemia: A Review |
title_sort | genetic manipulation strategies for β-thalassemia: a review |
topic | Pediatrics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9240386/ https://www.ncbi.nlm.nih.gov/pubmed/35783328 http://dx.doi.org/10.3389/fped.2022.901605 |
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