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体内递送编码单克隆抗体的 DNA 可保护非人灵长类动物免受寨卡病毒感染。

In Vivo Delivery of a DNA-Encoded Monoclonal Antibody Protects Non-human Primates against Zika Virus.

机构信息

Vaccine & Immunotherapy Center, The Wistar Institute of Anatomy & Biology, Philadelphia, PA, USA.

Humabs BioMed: a subsidiary of Vir Biotechnology, Bellinzona, Switzerland.

出版信息

Mol Ther. 2019 May 8;27(5):974-985. doi: 10.1016/j.ymthe.2019.03.005. Epub 2019 Apr 5.

DOI:10.1016/j.ymthe.2019.03.005
PMID:30962164
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6520333/
Abstract

Zika virus (ZIKV) infection is endemic to several world regions, and many others are at high risk for seasonal outbreaks. Synthetic DNA-encoded monoclonal antibody (DMAb) is an approach that enables in vivo delivery of highly potent mAbs to control infections. We engineered DMAb-ZK190, encoding the mAb ZK190 neutralizing antibody, which targets the ZIKV E protein DIII domain. In vivo-delivered DMAb-ZK190 achieved expression levels persisting >10 weeks in mice and >3 weeks in non-human primate (NHPs), which is protective against ZIKV infectious challenge. This study is the first demonstration of infectious disease control in NHPs following in vivo delivery of a nucleic acid-encoded antibody, supporting the importance of this new platform.

摘要

寨卡病毒（ZIKV）感染流行于世界多个地区，而许多其他地区也面临季节性爆发的高风险。合成 DNA 编码的单克隆抗体（DMAb）是一种能够将高效单克隆抗体递送至体内以控制感染的方法。我们构建了编码中和抗体 ZK190 的 DMAb-ZK190，该抗体针对 ZIKV E 蛋白 DIII 结构域。体内递送至小鼠体内的 DMAb-ZK190 表达水平持续超过 10 周，在非人类灵长类动物（NHPs）中持续超过 3 周，可预防 ZIKV 感染性挑战。这项研究首次证明了在体内递送至核酸编码抗体后，可在 NHPs 中控制传染病，支持了这一新平台的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebf3/6520333/1d8e017ffef3/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebf3/6520333/7a34253c1c24/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebf3/6520333/92278cc712b1/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebf3/6520333/3288ef8995d9/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebf3/6520333/1d8e017ffef3/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebf3/6520333/7a34253c1c24/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebf3/6520333/92278cc712b1/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebf3/6520333/3288ef8995d9/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebf3/6520333/1d8e017ffef3/gr4.jpg

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