Suppr超能文献

CRISPR/Cas 治疗策略治疗常染色体显性遗传病。

CRISPR/Cas therapeutic strategies for autosomal dominant disorders.

机构信息

Department of Biomedical Engineering and.

Jonas Children's Vision Care and Bernard and Shirlee Brown Glaucoma Laboratory, Columbia University, New York, New York, USA.

出版信息

J Clin Invest. 2022 May 2;132(9). doi: 10.1172/JCI158287.

Abstract

Autosomal dominant disorders present unique challenges, as therapeutics must often distinguish between healthy and diseased alleles while maintaining high efficiency, specificity, and safety. For this task, CRISPR/Cas remains particularly promising. Various CRISPR/Cas systems, like homology-directed repair, base editors, and prime editors, have been demonstrated to selectively edit mutant alleles either by incorporating these mutations into sgRNA sequences (near the protospacer-adjacent motif ["near the PAM"]) or by targeting a novel PAM generated by the mutation ("in the PAM"). However, these probability-based designs are not always assured, necessitating generalized, mutation-agnostic strategies like ablate-and-replace and single-nucleotide polymorphism editing. Here, we detail recent advancements in CRISPR therapeutics to treat a wide range of autosomal dominant disorders and discuss how they are altering the landscape for future therapies.

摘要

常染色体显性遗传病带来了独特的挑战,因为治疗方法必须在保持高效、特异性和安全性的同时,区分健康和病变等位基因。在这方面,CRISPR/Cas 仍然非常有前景。各种 CRISPR/Cas 系统,如同源定向修复、碱基编辑器和先导编辑,已经被证明可以通过将这些突变整合到 sgRNA 序列中(靠近原间隔基序[靠近 PAM])或通过靶向由突变产生的新 PAM(在 PAM 中),来选择性地编辑突变等位基因。然而,这些基于概率的设计并不总是确定的,因此需要像消融和替换以及单核苷酸多态性编辑这样的通用、无突变策略。在这里,我们详细介绍了 CRISPR 治疗在治疗广泛的常染色体显性遗传病方面的最新进展,并讨论了它们如何改变未来治疗的前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1eb8/9057583/a942ef823e80/jci-132-158287-g212.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验