NDLI: Editing aberrant splice sites efficiently restores β-globin expression in β-thalassemia

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Editing aberrant splice sites efficiently restores β-globin expression in β-thalassemia

Content Provider	Scilit
Author	Xu, Shuqian Luk, Kevin Yao, Qiuming Shen, Anne H. Zeng, Jing Wu, Yuxuan Luo, Hong-Yuan Brendel, Christian Pinello, Luca Chui, David H. K. Wolfe, Scot A. Bauer, Daniel E.
Copyright Year	2019
Description	The thalassemias are compelling targets for therapeutic genome editing in part because monoallelic correction of a subset of hematopoietic stem cells (HSCs) would be sufficient for enduring disease amelioration. A primary challenge is the development of efficient repair strategies that are effective in HSCs. Here, we demonstrate that allelic disruption of aberrant splice sites, one of the major classes of thalassemia mutations, is a robust approach to restore gene function. We target the IVS1-110G>A mutation using Cas9 ribonucleoprotein (RNP) and the IVS2-654C>T mutation by Cas12a/Cpf1 RNP in primary CD34+ hematopoietic stem and progenitor cells (HSPCs) from β-thalassemia patients. Each of these nuclease complexes achieves high efficiency and penetrance of therapeutic edits. Erythroid progeny of edited patient HSPCs show reversal of aberrant splicing and restoration of β-globin expression. This strategy could enable correction of a substantial fraction of transfusion-dependent β-thalassemia genotypes with currently available gene-editing technology.
Related Links	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6533605/pdf
Ending Page	2262
Page Count	8
Starting Page	2255
DOI	10.1182/blood-2019-01-895094
Journal	Blood
Issue Number	21
Volume Number	133
Language	English
Publisher	American Society of Hematology
Publisher Date	2019-05-23
Access Restriction	Open
Subject Keyword	Research and Experimental Medicine Hematopoietic Editing Correction Rnp Thalassemia Globin Restore Aberrant Hspcs Journal: Blood (Vol- 134, Issue- 21)
Content Type	Text
Resource Type	Article

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