한빛사논문
- 조회514
Byung-Chul Lee1, Richard J. Lozano1, Cynthia E. Dunbar1*
1Translational Stem Cell Biology Branch, National Heart, Lung, and Blood Institute, National
Institutes of Health, Bethesda, MD 20892, USA
*Correspondence
Abstract
Hematopoietic stem and progenitor cell (HSPC) gene therapies have recently moved beyond gene addition approaches to encompass targeted genome modification or correction, based on the development of zinc finger nucleases, TALENs and CRISPR/Cas technologies. Advances in ex vivo HSPC manipulation techniques have greatly improved HSPC susceptibility to genetic modification. Targeted gene editing techniques enable precise modifications at desired genomic sites. Numerous preclinical studies have already demonstrated the therapeutic potential of gene therapies based on targeted editing. However, several significant hurdles remain before broad clinical potential can be realized, related to adverse consequences of gene editing on HSPC function and genomic integrity. This review summarizes the status of HSPC gene editing, focusing on efficiency, genomic integrity, and long-term engraftment ability related to available genetic editing platforms and HSPC delivery methods. The response of long-term engrafting HSPCs to nuclease-mediated DNA breaks, with activation of p53, is a significant challenge, as are activation of innate and adaptive immune responses to editing components. Lastly, we propose alternative strategies that can overcome current hurdles to HSPC editing at various stages from cell collection to transplantation to facilitate successful clinical applications.
논문정보
- Review Paper
- 2021년 09월 (BRIC 등록일 2021-09-16)
- 국외 연구진
- 생명과학 > 분자생물학
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