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Retrovirology. 2018 Oct 1;15(1):66. doi: 10.1186/s12977-018-0449-7.

Adeno-associated virus gene delivery of broadly neutralizing antibodies as prevention and therapy against HIV-1.

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Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA.
Department of Systems Biology, Harvard University, Boston, MA, 02115, USA.
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA.


Vectored gene delivery of HIV-1 broadly neutralizing antibodies (bNAbs) using recombinant adeno-associated virus (rAAV) is a promising alternative to conventional vaccines for preventing new HIV-1 infections and for therapeutically suppressing established HIV-1 infections. Passive infusion of single bNAbs has already shown promise in initial clinical trials to temporarily decrease HIV-1 load in viremic patients, and to delay viral rebound from latent reservoirs in suppressed patients during analytical treatment interruptions of antiretroviral therapy. Long-term, continuous, systemic expression of such bNAbs could be achieved with a single injection of rAAV encoding antibody genes into muscle tissue, which would bypass the challenges of eliciting such bNAbs through traditional vaccination in naïve patients, and of life-long repeated passive transfers of such biologics for therapy. rAAV delivery of single bNAbs has already demonstrated protection from repeated HIV-1 vaginal challenge in humanized mouse models, and phase I clinical trials of this approach are underway. Selection of which individual, or combination of, bNAbs to deliver to counter pre-existing resistance and the rise of escape mutations in the virus remains a challenge, and such choices may differ depending on use of this technology for prevention versus therapy.


AAV; Animal models; Antibody gene transfer; Clinical trials; HIV-1; Vectored delivery; bNAb

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