AAV5 Delivery of CRISPR/Cas9 Mediates Genome Editing in the Lungs of Young Rhesus Monkeys.

IF 3.9 3区 医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Human gene therapy Pub Date : 2024-10-01 Epub Date: 2024-07-03 DOI:10.1089/hum.2024.035
Shun-Qing Liang, Andrew W Navia, Michelle Ramseier, Xuntao Zhou, Michele Martinez, Charles Lee, Chen Zhou, Joae Wu, Jun Xie, Qin Su, Dan Wang, Terence R Flotte, Daniel G Anderson, Alice F Tarantal, Alex K Shalek, Guangping Gao, Wen Xue
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引用次数: 0

Abstract

Genome editing has the potential to treat genetic diseases in a variety of tissues, including the lung. We have previously developed and validated a dual adeno-associated virus (AAV) CRISPR platform that supports effective editing in the airways of mice. To validate this delivery vehicle in a large animal model, we have shown that intratracheal instillation of CRISPR/Cas9 in AAV5 can edit a housekeeping gene or a disease-related gene in the lungs of young rhesus monkeys. We observed up to 8% editing of angiotensin-converting enzyme 2 (ACE2) in lung lobes after single-dose administration. Single-nuclear RNA sequencing revealed that AAV5 transduces multiple cell types in the caudal lung lobes, including alveolar cells, macrophages, fibroblasts, endothelial cells, and B cells. These results demonstrate that AAV5 is efficient in the delivery of CRISPR/Cas9 in the lung lobes of young rhesus monkeys.

AAV5输送CRISPR/Cas9介导幼年恒河猴肺部基因组编辑。
基因组编辑有可能治疗包括肺部在内的各种组织的遗传疾病。我们之前开发并验证了一种双重腺相关病毒(AAV)CRISPR 平台,该平台支持在小鼠气道中进行有效编辑。为了在大型动物模型中验证这种递送载体,我们证明了气管内灌注AAV5中的CRISPR/Cas9可以编辑幼年恒河猴肺部的看家基因或疾病相关基因。我们观察到,单剂量给药后,肺叶中 ACE2 的编辑率高达 8%。单核 RNA 序列测定显示,AAV5 可转导尾部肺叶中的多种细胞类型,包括肺泡细胞、巨噬细胞、成纤维细胞、内皮细胞和 B 细胞。这些结果表明,AAV5 能在幼年恒河猴的肺叶中有效传递 CRISPR/Cas9。
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来源期刊
Human gene therapy
Human gene therapy 医学-生物工程与应用微生物
CiteScore
6.50
自引率
4.80%
发文量
131
审稿时长
4-8 weeks
期刊介绍: Human Gene Therapy is the premier, multidisciplinary journal covering all aspects of gene therapy. The Journal publishes in-depth coverage of DNA, RNA, and cell therapies by delivering the latest breakthroughs in research and technologies. Human Gene Therapy provides a central forum for scientific and clinical information, including ethical, legal, regulatory, social, and commercial issues, which enables the advancement and progress of therapeutic procedures leading to improved patient outcomes, and ultimately, to curing diseases.
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