Although we call the triple drug therapy can keep HIV count a patient under control for years, only one or two mutations in the genome the virus can cause resistance to develop and begin to multiply again. A paper Nature Medicine describes a potential drug can be much harder to thwart today :. A killer protein with a molecular booby trap to destroy the infected cells
The most effective drugs against HIV block an enzyme called protease that helps the virus to build new satellite particles. A group led by Steven Dowdy, a molecular oncologist at Washington University in St. Louis, decided to try another approach: Instead of blocking protease, they hope to turn against HIV. Their strategy is to trick the virus using its protease to open a deadly package in the cells it infects. "We designed a Trojan molecule," said Dowdy.
The packet contains a lethal protein called caspase 3, an enzyme which when cleaved apart, can pass on a cell suicide machines. To limit this destruction of infected cells, the researchers modified cleavage sites to those recognized by the HIV protease. They also include a molecular skeleton key, a protein called TAT allows the assembly enter cells. In cultures of human T cells, the molecule killed 75% of the cells infected with HIV in 16 hours. The team has already authorized the development IDUN Pharmaceuticals in La Jolla, California.
Some scholars believe, however, that the molecular Trojan horse may have a fatal weakness. The protein should be injected into the bloodstream, where it "is likely to induce an immune response and be removed before it is to infected cells," said virologist Nava Sarver of the National Institute of Allergy and Infectious Diseases . Sarver is more optimistic about the idea of Dowdy to adapt the strategy for the treatment of localized prostate cancer, using a TAT / caspase which can be activated by tumor cells.
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