对CRISPR Cas9和Cas12a疗法的免疫。

IF 7.9 Q1 Medicine Wiley Interdisciplinary Reviews-Systems Biology and Medicine Pub Date : 2018-01-01 Epub Date: 2017-10-30 DOI:10.1002/wsbm.1408
Wei Leong Chew
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引用次数: 97

摘要

基因组编辑疗法有望治疗人类疾病。随着最有前景的 CRISPR-Cas9 和 CRISPR-Cas12a (Cpf1) 模式进入临床试验阶段,向人类患者施用这些外来生物分子的相关风险日益突出。CRISPR-Cas9和CRISPR-Cas12a系统的临床前发现和基础基因治疗研究表明,宿主免疫系统会对施用的蛋白质和核酸、基因编辑细胞以及宿主本身产生不良反应。这些宿主防御措施包括通过激活先天性免疫引起的炎症、体液免疫中的抗体诱导以及 T 细胞介导的细胞毒性造成的细胞死亡。如果任其发展,这些免疫反应会影响治疗效果,并可能导致死亡。因此,检测和降低 Cas9 和 Cas12a 蛋白免疫原性的方法对于确保患者安全和治疗效果,以及让我们更接近实现永久性基因治疗的愿景至关重要。WIREs Syst Biol Med 2018, 10:e1408. doi: 10.1002/wsbm.1408 本文归类于:实验室方法和技术 > 基因/基因组方法 转化、基因组和系统医学 > 转化医学 转化、基因组和系统医学 > 治疗方法。
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Immunity to CRISPR Cas9 and Cas12a therapeutics.

Genome-editing therapeutics are poised to treat human diseases. As we enter clinical trials with the most promising CRISPR-Cas9 and CRISPR-Cas12a (Cpf1) modalities, the risks associated with administering these foreign biomolecules into human patients become increasingly salient. Preclinical discovery with CRISPR-Cas9 and CRISPR-Cas12a systems and foundational gene therapy studies indicate that the host immune system can mount undesired responses against the administered proteins and nucleic acids, the gene-edited cells, and the host itself. These host defenses include inflammation via activation of innate immunity, antibody induction in humoral immunity, and cell death by T-cell-mediated cytotoxicity. If left unchecked, these immunological reactions can curtail therapeutic benefits and potentially lead to mortality. Ways to assay and reduce the immunogenicity of Cas9 and Cas12a proteins are therefore critical for ensuring patient safety and treatment efficacy, and for bringing us closer to realizing the vision of permanent genetic cures. WIREs Syst Biol Med 2018, 10:e1408. doi: 10.1002/wsbm.1408 This article is categorized under: Laboratory Methods and Technologies > Genetic/Genomic Methods Translational, Genomic, and Systems Medicine > Translational Medicine Translational, Genomic, and Systems Medicine > Therapeutic Methods.

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来源期刊
CiteScore
18.40
自引率
0.00%
发文量
0
审稿时长
>12 weeks
期刊介绍: Journal Name:Wiley Interdisciplinary Reviews-Systems Biology and Medicine Focus: Strong interdisciplinary focus Serves as an encyclopedic reference for systems biology research Conceptual Framework: Systems biology asserts the study of organisms as hierarchical systems or networks Individual biological components interact in complex ways within these systems Article Coverage: Discusses biology, methods, and models Spans systems from a few molecules to whole species Topical Coverage: Developmental Biology Physiology Biological Mechanisms Models of Systems, Properties, and Processes Laboratory Methods and Technologies Translational, Genomic, and Systems Medicine
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