Matthew R. Gardner, Lisa M. Kattenhorn, Hema R. Kondur, Markus von Schaewen, Tatyana Dorfman, Jessica J. Chiang, Kevin G. Haworth, Julie M. Decker, Michael D. Alpert, Charles C. Bailey, Ernest S. Neale Jr, Christoph H. Fellinger, Vinita R. Joshi, Sebastian P. Fuchs, Jose M.Martinez-Navio, Brian D.Quinlan, Annie Y.Yao, Hugo Mouquet, Jason Gorman, Baoshan Zhang, Pascal Poignard, Michel C. Nussenzweig, Dennis R. Burton, Peter D. Kwong, Michael Piatak Jr, Jeffrey D. Lifson, Guangping Gao, Ronald C. Desrosiers, David T. Evans, Beatrice H. Hahn, Alexander Ploss, Paula M. Cannon, Michael S. Seaman, Michael Farzan
Nature. 2015 Mar 5;519(7541):87-91.
By combining the parts of CD4 and CCR5 that are recognized by HIV onto a single synthetic antibody, eCD4-Ig disarms the features of HIV that allow it to resist antibodies that might otherwise interfere with receptor recognition and infection of susceptible T cells. Because eCD4-Ig is based on the receptor and co-receptor structures recognized by HIV, it recognizes all strains of HIV.
A one-time administration of AAV vectors expressing eCD4-Ig protected rhesus macaques from infection despite multiple intravenous challenges with simian/human immunodeficiency virus (SHIV).
Guocai Zhong, Haimin Wang, Wenhui He, Yujun Li, Huihui Mou, Zachary J. Tickner, Mai H. Tran, Tianling Ou, Yiming Yin, Huitian Diao & Michael Farzan
Nat Biotechnol. 2019 Dec 23 [Epub ahead of print]
Emmune cofounder Guocai Zhong and colleagues have developed a means of turning on and off (or modulating up and down) a gene therapy.
Guocai Zhong, Haimin Wang, Yujun Li, Mai H Tran, Michael Farzan
Nat Chem Biol. 2017 Aug;13(8):839-841.
We are developing off-switches for AAV vectors. In this publication, we show that Cpf1 can inactivate a target gene when its guide RNA is expressed from an RNA Polymerase II promoter in mammalian cells.
Ina Fetzer, Matthew R. Gardner, Meredith E. Davis-Gardner, Neha R. Prasad, Barnett Alfant, Jesse A. Weber, Michael Farzan
J Virol. 2018 May 29;92(12).
The potency with which eCD4-Ig neutralizes virus infection was increased by 10-fold.
Matthew R. Gardner, Christoph H. Fellinger, Lisa M. Kattenhorn, Meredith E. Davis-Gardner, Jesse A. Weber, Barnett Alfant, Amber S. Zhou, Neha R. Prasad, Hema R. Kondur, Wendy A. Newton, Kimberly L. Weisgrau, Eva G. Rakasz, Jeffrey D. Lifson, Guangping Gao, Nancy Schultz-Darken and Michael Farzan
Sci Transl Med. 2019 Jul 24;11(502).
AAV-delivered eCD4-Ig prevented monkeys from becoming infected with intravenous doses of SIVmac239 that infected all of the untreated control monkeys. SIVmac239 is thought to be a realistic model for HIV infection in humans. Further escalating the dose of SIVmac239 infused intravenously into the AAV/eCD4-Ig monkeys did eventually result in their infection. This level of protection against infection with SIVmac239 is unprecedented by vaccine strategies that are under consideration for use in humans.
Meredith E. Davis-Gardner, Matthew R. Gardner, Barnett Alfant, Michael Farzan
PLoS Pathog. 2017 Dec 18;13(12):e1006786.
eCD4-Ig directs the killing of HIV-infected cells by natural killer (NK) cells by antibody-dependent cell-mediated cytotoxicity (ADCC). Here, eCD4-Ig was shown to further enhance efficient killing of HIV-infected cells by ADCC by exposing HIV to host antibodies.
Christoph H. Fellinger, Matthew R. Gardner, Jesse A. Weber, Barnett Alfant, Amber S. Zhou, Michael Farzan
J Virol. 2019 Jun 28;93(14).
Culturing virus in the presence of eCD4-Ig, CD4-Ig, or a broadly neutralizing antibody for most of a year selected for complete escape of CD4-Ig and the broadly neutralizing antibody but not eCD4-Ig.
Matthew R. Gardner, Ina Fetzer, Lisa M. Kattenhorn, Meredith E. Davis-Gardner, Amber S. Zhou, Barnett Alfant, Jesse A. Weber, Hema R. Kondur, Jose M. Martinez-Navio, Sebastian P. Fuchs, Ronald C. Desrosiers, Guangping Gao, Jeffrey D. Lifson, Michael Farzan
Mol Ther. 2019 Mar 6;27(3):650-660.
When delivered by AAV vectors, broadly neutralizing antibodies become targets for immune responses. Such immune responses targeting broadly neutralizing antibodies limit their efficacy.