基于 CRISPR 的治疗性基因组编辑：策略和 AAV 载体的体内递送。
CRISPR-Based Therapeutic Genome Editing: Strategies and In Vivo Delivery by AAV Vectors.
机构信息
Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA 01605, USA; RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Brain and Cognitive Sciences, Department of Biological Engineering, McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Cambridge, MA 02139, USA.
出版信息
Cell. 2020 Apr 2;181(1):136-150. doi: 10.1016/j.cell.2020.03.023.
Abstract
The development of clustered regularly interspaced short-palindromic repeat (CRISPR)-based biotechnologies has revolutionized the life sciences and introduced new therapeutic modalities with the potential to treat a wide range of diseases. Here, we describe CRISPR-based strategies to improve human health, with an emphasis on the delivery of CRISPR therapeutics directly into the human body using adeno-associated virus (AAV) vectors. We also discuss challenges facing broad deployment of CRISPR-based therapeutics and highlight areas where continued discovery and technological development can further advance these revolutionary new treatments.
摘要
基于成簇规律间隔短回文重复序列（CRISPR）的生物技术的发展彻底改变了生命科学，并引入了新的治疗模式，有可能治疗广泛的疾病。在这里，我们描述了基于 CRISPR 的策略来改善人类健康，重点是使用腺相关病毒（AAV）载体将 CRISPR 治疗剂直接递送到人体中。我们还讨论了在广泛部署基于 CRISPR 的治疗方法时面临的挑战，并强调了继续发现和技术发展可以进一步推进这些革命性新疗法的领域。
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Sci Adv. 2020 Feb 12;6(7):eaax5701. doi: 10.1126/sciadv.aax5701. eCollection 2020 Feb.
2
The promise and challenge of therapeutic genome editing.治疗性基因组编辑的前景与挑战。
Nature. 2020 Feb;578(7794):229-236. doi: 10.1038/s41586-020-1978-5. Epub 2020 Feb 12.
3
Treatment of a Mouse Model of ALS by In Vivo Base Editing.体内碱基编辑治疗肌萎缩侧索硬化症小鼠模型。
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Nat Cell Biol. 2019 Dec;21(12):1468-1478. doi: 10.1038/s41556-019-0425-z. Epub 2019 Dec 2.
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