One of the biggest difficulties with this process is finding a suitable transport agent that can carry the nucleic acid being used as a "drug" into the diseased target cell. Killed viruses have been used as "taxis" for these genes, but these often have unexpected health consequences.

Recently, nanoparticles have been developed for gene therapy. A successful example of this has been described by V. M. Rotello, N. S. Forbes, and their co-workers in Massachusetts, USA. They used tiny spheres of gold with tightly packed, positively charged hydrocarbon chains bound to their surface. These chains contain a photolabile bond that is stable to visible light but breaks when irradiated with UV light at a wavelength of 350 nm. This causes the positively charged fragment to fall off, leaving the gold sphere with a negative charge on its surface.

DNA contains negatively charged phosphate groups that allow it to bind to the positively charged gold spheres through electrostatic interactions. Cells that were brought into contact with gold spheres loaded with DNA allowed these "DNA taxis" to pass into their interior. The signal to "unload" was given by subsequent irradiation with UV light: it destroyed the photolabile bond, reversing the surface charge of the gold particles and releasing the DNA. Fortunately, the DNA was not only brought into the cytoplasm; it made its way to where it was needed: the cell nucleus. This is the location in the cell where DNA molecules are copied for translation into proteins or are multiplied for cell division.

This process offers a relatively simple possibility for the transport and controlled release of DNA into living cells. In addition, the authors believe that this method should make it possible to steer interactions with other biomolecules, such as proteins or pharmaceutical agents, making it possible to target specific cells.

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"Since the epidemic began 25 years ago, only about 1,000 people in the earliest stages of HIV infection have been identified," Cohen said. "Even more troubling, only a handful of transmission pairs have been reported. CHAVI has the resources to find them in substantial numbers."

According to Cohen, knowledge of the viral requirements for transmission is crucial to understanding how to make a vaccine against HIV. That's why one needs HIV both from the recipient and the person who transmitted it.

Also important to vaccine development is knowledge of the immunological environment in which transmission occurred, Cohen said. This means determining as close as possible to the time of transmission the kind of immune defenses that can restrain viral replication.

"We know that while the host defenses are not going to eliminate the virus, they can achieve some measure of control," Cohen said. "When the control is achieved, the viral growth level is called the 'set point.' We know that people who've achieved a lower set point - that is, better control of their virus - are likely on average to live longer healthier lives and seem to be less likely to transmit the virus to their sexual partners."

Cohen said that along with studying the virus and immunological defenses, CHAVI also has the resources to study genetic factors that may be involved in HIV acquisition, including host genetic factors influencing infection and early progression of HIV-1 disease.

"CHAVI-001 will probably be able to study enough people so that genetics and the genetics of HIV acquisition and set points can be investigated."

There are six sites for CHAVI-001: in Malawi, one in Llongwe and one in Blantyre; in South Africa, one in Johannesburg and one in Durban; and in North Carolina, one at UNC and one at Duke.

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