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

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...

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Detalles Bibliográficos
Autores principales: Esquivel, Rianne N., Patel, Ami, Kudchodkar, Sagar B., Park, Daniel H., Stettler, Karin, Beltramello, Martina, Allen, Jeffrey W., Mendoza, Janess, Ramos, Stephanie, Choi, Hyeree, Borole, Piyush, Asija, Kanika, Bah, Mamadou, Shaheen, Shareef, Chen, Jing, Yan, Jian, Durham, Amy C., Smith, Trevor R.F., Broderick, Kate, Guibinga, Ghiabe, Muthumani, Kar, Corti, Davide, Humeau, Laurent, Weiner, David B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2019
Materias:
Original Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6520333/
https://www.ncbi.nlm.nih.gov/pubmed/30962164
http://dx.doi.org/10.1016/j.ymthe.2019.03.005
Descripción
Sumario: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.

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