Cyanovirins and Related Conjugates, Compositions, Nucleic Acids, Vectors, Host Cells, Methods of Production and Methods of Use f
Posted Jun 15 2010 5:00pm
Description of Invention: The development of an effective anti-HIV topical microbicide, especially a female-controlled, vaginal microbicide, has been deemed an urgent global priority by numerous international agencies, including the World Health Organization, the U.S. Department of Health and Human Services, the National Institute of Allergy and Infectious Diseases, and others. The present invention provides antiviral proteins (collectively referred to as cyanovirins), conjugates thereof, DNA sequences encoding such agents, host cells containing such DNA sequences, antibodies directed to such agents, compositions comprising such agents, and methods of obtaining and using such agents for the production of microbicides.
Cyanovirin-N (CV-N) potently and irreversibly inactivates diverse primary strains of HIV-1, including M-tropic forms involved in sexual transmission of HIV, as well as T-tropic and dual-tropic forms; CV-N also blocks cell-to-cell transmission of HIV infection. CV-N is directly virucidal, interacting in an unusual manner with the viral envelope, apparently binding with extremely high affinity to poorly immunogenic epitopes on gp120. Further, cyanovirin-N (CV-N) and homologous proteins and peptides potently inhibit diverse isolates of influenza viruses A and B, the two major types of influenza virus that infect humans.
The described technology includes glycosylation-resistant mutants of CV-N, which code sequences to enable ultra large-scale recombinant production of functional cyanovirins in non-bacterial (yeast or insect) host cells or in transgenic animals or plants. Therefore, these glycosylation-resistant mutants may allow industry to produce CV-Ns on a large scale and make CV-Ns cheap enough for developing countries to benefit from this invention.
CV-N was benign in vivo when tested in the rabbit vaginal toxicity/irritancy model, and was not cytotoxic in vitro against human immune cells and lactobacilli (unpublished). CV-N is readily soluble in aqueous media, is remarkably resistant to physicochemical degradation and is amenable to very large-scale production by a variety of genetic engineering approaches.
Applications: Development of microbicides against HIV and influenza
Development Status: Preclinical data is available at this time
Inventors: Michael R Boyd (NCI) Robert H Shoemaker (NCI) Toshiyuki Mori (NCI) Angela M Gronenborn (NIDDK)
Patent Status: HHS, Reference No. E-074-1999/2 PCT, Application No. PCT/US00/06247 filed 10 Mar 2000 ; National Stage Filing in United States, Japan, Australia, Europe, Germany, France, China, United Kingdom, and Belgium
B Giomarelli, R Provvedi, F Meacci, T Maggi, D Medaglini, G Pozzi, T Mori, JB McMahon, R Gardella, MR Boyd. The microbicide cyanovirin-N expressed on the surface of commensal bacterium Streptococcus gordonii captures HIV-1. AIDS. 2002 Jul 5;16(10):1351-1356. [ PubMed abs ]
CC Tsai, P Emau, Y Jiang, MB Agy, RJ Shattock, A Schmidt, WR Morton, KR Gustafson, MR Boyd. Cyanovirin-N inhibits AIDS virus infections in vaginal transmission models. AIDS Res Hum Retroviruses. 2004 Jan;20(1):11-18. [ PubMed abs ]
Licensing Status: Available for licensing and commercial development.
Collaborative Research Opportunity: The National Cancer Institute’s Molecular Targets Development Program is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize microbicides for HIV and influenza. Please contact John D. Hewes at (301) 435-3121 or email@example.com for more information.
Portfolios: Infectious Diseases Infectious Diseases - Therapeutics In-vivo Data
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