Molecular Targets Development Program

The MTDP is cooperating with the National Library of Medicine to post data from our high throughput screens within PubChem, an important element of the NIH Roadmap. Data will be posted for all public compounds once screening projects are complete. The first screen to be posted will be data for the HIV-1 RNase H, a collaboration with Stuart Le Grice and Michael Parniak.

An award has been assigned to the Poster Presentation “Mucosal Delivery of Microbicides by Commensal Bacteria” illustrating results of a research project in collaboration between the MTDP (NCI, CCR) and the Dep. of Molecular Biology of the University of Siena, Italy. The award has been handed  over to the poster authors personally by the Princess Royal during the official ceremony at the Microbicides 2004 Conference that has taken place in London (28-31 March 2004). 764 delegates from 52 countries attended the conference, which has reported novel and innovative works in the microbicides field and provided opportunities for knowledge sharing between microbicide researchers and public-health organizations.

Cyanovirin-N (CV-N), a potent HIV-inactivating protein, was originally discovered from the cyanobacterium (blue-green alga) Nostoc ellipsosporum in the previous incarnation of the MTDP at the NCI [1]. It has been demonstrated that CV-N gel as a topical microbicide can prevent rectal and vaginal transmission of a pathogenic chimeric SIV/HIV-1 virus (SHIV) in macaques without cytotoxic or clinical adverse effects [2, 3]. These studies encourage clinical evaluation of CV-N as a topical microbicide to prevent sexual transmisision of HIV in humans.  

An effective CV-N-based microbicide may require long-term presence or continuous delivery of CV-N at the potential mucosal sites of entry of HIV. One approach to this need is the endogenous production of virucidal concentrations of CV-N at mucosal surfaces by a colonizing commensal bacterium [4]. The Poster Presentation illustrated the feasibility to express CV-N in the commensal bacterium Streptococcus gordonii in a recombinant form that was active as the native protein, and the development of a genetic system to stably express CV-N and other microbicides in different Lactobacillus strains, which are suitable for long-term vaginal colonization.

References

1. Antimicrob. Agents Chemother. 41: 1521-30, 1997.

2. AIDS Res. Hum. Retroviruses 19: 535-41, 2003.

3. AIDS Res. Hum. Retroviruses 20: 11-8, 2004.

4. AIDS 16: 1351-6, 2002.

© 2000-2005 Center for Cancer Research at the National Cancer Institute.
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Last modified November 14, 2005

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