An exhaustive body of data has been generated that indicates the importance of efforts to further develop cyanovirin-N (CV-N) as an anti-HIV-1 microbicide. It is a highly potent inhibitor of cell-free and cell-to-cell transmission of HIV-1 infection, with no observable toxic effect on host cells. The primary obstacle to advancing CV-N as a microbicide is the fact that it is currently difficult to produce in quantities required for proper preclinical study and clinical evaluation. As a recombinant protein, CV-N must be produced by means of an in vivo recombinant expression system. Our central hypothesis in this Project is that being of prokaryotic origin, CV-N should be highly compatible with bacteria-based expression systems, and its unique biochemical properties make it feasible to apply an array of purification technologies that typically would not be appropriate in efforts to obtain a bioactive recombinant protein. Therefore, we have defined a set of Specific Aims that are designed to: (1) comprehensively study the regulation of CV-N expression in bacterial systems; (2) exploit the unique biochemical properties of CV-N in the development of a high yield purification scheme; (3) determine the relevance of specific growth parameters to the expression of CV-N in larger scale fermentation; and (4) test if alternative forms of CV-N can be engineered that either enhance production or HIV-1 inhibitory activity. These efforts will be achieved through extensive interaction between the research team of this project, and the other Research Projects and Cores of the Program.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
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Special Emphasis Panel (ZAI1)
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Biosyn, Inc.
Huntingdon Valley
United States
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