In vivo delivery of synthetic DNA–encoded antibodies induces broad HIV-1– neutralizing activity Megan C. Wise, … , Laurent M. Humeau, David B. Weiner J Clin Invest. 2020;130(2):827-837. https://doi.org/10.1172/JCI132779 1 Inovio Pharmaceuticals, Plymouth Meeting, Pennsylvania, USA. 2 Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, Pennsylvania, USA. 3 Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 4 Duke Human Vaccine Institute and 5 Department of Surgery, Duke University School of Medicine, Durham, North Carolina, USA.
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 that possess the characteristics necessary for potential prophylactic or therapeutic approaches. However, formulation complexities, especially for multiantibody deliveries, long infusion times, and production issues could limit the use of these bNAbs when deployed, globally affecting 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 dmAb cassettes and studied their activity in small and large animals. Sera from animals administered dmAbs neutralized multiple HIV-1 isolates with activity similar to that of their parental recombinant mAbs. Delivery of multiple dmAbs to a single animal led to increased neutralization breadth. Two dmAbs, PGDM1400 and PGT121, were advanced into nonhuman primates for study. High peak-circulating levels (between 6 and 34 μg/ml) of these dmAbs were measured, and the sera of all animals displayed broad neutralizing activity. The dmAb approach provides an important local delivery platform for the in vivo generation of HIV-1 bNAbs and for other infectious disease antibodies. https://www.jci.org/articles/view/132779/pdf
所以我不太信季博士那个肌肉注射抗新冠DNA抗体无效，这是最新前沿科技。
In vivo delivery of synthetic DNA–encoded antibodies induces broad HIV-1–
neutralizing activity
Megan C. Wise, … , Laurent M. Humeau, David B. Weiner
J Clin Invest. 2020;130(2):827-837. https://doi.org/10.1172/JCI132779
1
Inovio Pharmaceuticals, Plymouth Meeting, Pennsylvania, USA. 2
Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia,
Pennsylvania, USA. 3
Perelman School of Medicine, University of
Pennsylvania, Philadelphia, Pennsylvania, USA. 4
Duke Human Vaccine Institute and 5
Department of Surgery, Duke University School of Medicine, Durham, North
Carolina, USA.
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 that possess the characteristics necessary for
potential
prophylactic or therapeutic approaches. However, formulation complexities,
especially for
multiantibody deliveries, long infusion times, and production issues could
limit the use of
these bNAbs when deployed, globally affecting 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 dmAb cassettes and studied their activity in small and large
animals. Sera from
animals administered dmAbs neutralized multiple HIV-1 isolates with activity similar to that
of their parental recombinant mAbs. Delivery of multiple dmAbs to a single
animal led to
increased neutralization breadth. Two dmAbs, PGDM1400 and PGT121, were
advanced
into nonhuman primates for study. High peak-circulating levels (between 6
and 34 μg/ml) of
these dmAbs were measured, and the sera of all animals displayed broad
neutralizing
activity. The dmAb approach provides an important local delivery platform
for the in vivo
generation of HIV-1 bNAbs and for other infectious disease antibodies.
https://www.jci.org/articles/view/132779/pdf