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In vivo delivery of synthetic DNA-encoded antibodies induces broad HIV-1-neutralizing activity.

J Clin Invest. 2019-11; 
Megan C Wise, Ziyang Xu, Edgar Tello-Ruiz, Charles Beck, Aspen Trautz, Ami Patel, Sarah Tc Elliott, Neethu Chokkalingam, Sophie Kim, Melissa G Kerkau, Kar Muthumani, Jingjing Jiang, Paul Fisher, Stephany J Ramos, Trevor Rf Smith, Janess Mendoza, Kate E Broderick, David C Montefiori, Guido Ferrari, Daniel W Kulp, Laurent Humeau, David B Weiner
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Gene Synthesis The heavy and light chain were synthesized and cloned (Genscript) into a modified mammalian pVAX1 expression plasmid (ThermoFisher)...Binding curves of HIV serum-expressed dMAbs compared to recombinant proteins were obtained by coating 96 well half-area high binding polystyrene plates (ThermoFisher) with 1µg/ml of rabbit anti-His antibody (25B6E11, Genscript) in PBS at 4 ℃. Get A Quote
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摘要

Interventions to prevent HIV-1 infection and alternative tools in HIV cure therapy remain pressing goals. Recently, numerous broadly neutralizing HIV-1 monoclonal antibodies (bNAbs) have been developed which possess the characteristics necessary for potential prophylactic or therapeutic approaches. However, formulation complexities especially for multi-antibody deliveries, long infusion times, and production issues could limit the use of these bNAbs when deployed globally impacting their potential application. Here, we describe an approach utilizing synthetic DNA-encoded monoclonal antibodies (dMAbs) for direct in vivo production of prespecified neutralizing activity. We designed 16 different bNAbs as dMAbs cas... More

关键词

AIDS/HIV; Gene therapy; Immunology; Immunotherapy.
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