Engineered deletions of HIV replicate conditionally to reduce disease in nonhuman primates-Reference-Cited by-同舟云学术

Engineered deletions of HIV replicate conditionally to reduce disease in nonhuman primates

Published:2024-08-09 Issue:6709 Volume:385 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Pitchai Fathima N. Nagoor¹²,Tanner Elizabeth J.¹²,Khetan Neha¹²,Vasen Gustavo¹²,Levrel Clara¹²,Kumar Arjun J.¹²³,Pandey Shilpi⁴,Ordonez Tracy⁴,Barnette Philip⁴,Spencer David⁴⁵,Jung Seung-Yong¹,Glazier Joshua¹,Thompson Cassandra¹⁶,Harvey-Vera Alicia,Son Hye-In⁷⁸⁹,Son Hye-In¹,Strathdee Steffanie A.⁷,Holguin Leo⁷,Urak Ryan¹⁰,Burnett John¹⁰¹¹,Burgess William⁹,Busman-Sahay Kathleen⁹,Estes Jacob D.⁹¹²¹³,Hessell Ann⁴,Fennessey Christine M.¹⁴,Keele Brandon F.¹⁴,Haigwood Nancy L.⁴,Weinberger Leor S.¹²¹⁵¹⁶

Affiliation:

1. Gladstone Center for Cell Circuitry, University of California, San Francisco, CA, USA.

2. Gladstone Institute of Virology, University of California, San Francisco, CA, USA.

3. Department of Bioengineering, University of Washington, Seattle, WA, USA.

4. Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, USA.

5. Absci Corporation, Vancouver, WA, USA.

6. Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.

7. Global Health Sciences, Department of Medicine, University of California San Diego, La Jolla, CA, USA.

8. US-Mexico Border Health Commission, Tijuana, Mexico.

9. Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR, USA.

10. Center for Gene Therapy, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA.

11. Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL, USA.

12. Faculty of Health, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.

13. School of Health and Biomedical Sciences College of Science, Engineering and Health RMIT University, Melbourne, Australia.

14. AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.

15. Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.

16. Department 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 [R 0 ] > 1 (termed “therapeutic interfering particles” or “TIPs”), could parasitize wild-type virus to constitute single-administration, escape-resistant antiviral therapies. We report the engineering of a TIP that, in rhesus macaques, reduces viremia of a highly pathogenic model of HIV by >3log 10 following a single intravenous injection. Animal lifespan was significantly extended, TIPs conditionally replicated and were continually detected for >6 months, and sequencing data showed no evidence of viral escape. A single TIP injection also suppressed virus replication in humanized mice and cells from persons living with HIV. These data provide proof of concept for a potential new class of single-administration antiviral therapies.

Publisher

American Association for the Advancement of Science (AAAS)

Link

https://www.science.org/doi/pdf/10.1126/science.adn5866

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