Peer-Reviewed Publication
Science2024;385(6709):eadn5866.August 9, 2024Journal Article
Engineered deletions of HIV replicate conditionally to reduce disease in nonhuman primates.
Fathima N Nagoor Pitchai1,2, Elizabeth J Tanner1,2, Neha Khetan1,2, Gustavo Vasen1,2, Clara Levrel1,2, Arjun J Kumar1,2,3, Shilpi Pandey4, Tracy Ordonez4, Philip Barnette4, David Spencer4,5, Seung-Yong Jung1, Joshua Glazier1, Cassandra Thompson1,6, Alicia Harvey-Vera, Hye-In Son7,8,9, Hye-In Son1, Steffanie A Strathdee7, Leo Holguin7, Ryan Urak10, John Burnett10,11, William Burgess9, Kathleen Busman-Sahay9, Jacob D Estes9,12,13, Ann Hessell4, Christine M Fennessey14, Brandon F Keele14, Nancy L Haigwood4, Leor S Weinberger1,2,15,16
1Gladstone Center for Cell Circuitry, University of California, San Francisco, CA, USA.
2Gladstone Institute of Virology, University of California, San Francisco, CA, USA.
3Department of Bioengineering, University of Washington, Seattle, WA, USA.
4Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, USA.
5Absci Corporation, Vancouver, WA, USA.
6Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.
7Global Health Sciences, Department of Medicine, University of California San Diego, La Jolla, CA, USA.
8US-Mexico Border Health Commission, Tijuana, Mexico.
9Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR, USA.
10Center for Gene Therapy, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA.
11Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL, USA.
12Faculty of Health, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
13School of Health and Biomedical Sciences College of Science, Engineering and Health RMIT University, Melbourne, Australia.
14AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
15Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.
16Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.
Abstract
Antiviral therapies with reduced frequencies of administration and high barriers to resistance remain a major goal. For HIV, theories have proposed that viral-deletion variants, which conditionally replicate with a basic reproductive ratio [R0] > 1 (termed "therapeutic interfering particles" or "TIPs"), could parasitize wild-type virus to constitute single-administration, escape-resistant antivira…
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