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Transforming Cells into Molecular Assassins
The conventional approach to vaccination involves training the immune system to fight an infection. But the Researchers at Scripps Research Institute in California have derived a new technique that involves altering the DNA in order to give cells anti-HIV capabilities. A discovery that potentially could lead to a new therapy for patients as well as an alternative to a vaccine.
Problem with HIV
Usually when a cell has been infected by a virus, enzymes chop up the viral proteins into short peptides which combine with HLA proteins in Endoplasmic reticulum. These are then transferred to the surface of the infected cell, labelling the cell as threat but HIV being a highly variable virus has found a way to fool our Immune system by interfering with the binding process. The virus accumulates mutations in it viral proteins thus rendering them unable to bind to the HLA proteins or resulting in very weak binding. Hence effectively putting the T-cells out of action. Moreover HIV fuses with the cell and inserts its own genetic material i.e. a single-stranded RNA and transforms the host cell into a HIV manufacturing site.
Scripp’s Radical Approach
Researchers at Scripps Research Institute in California have successfully altered the DNA of monkeys to give their cells HIV-fighting properties. The technique involved using engineered Adeno-associated virus to introduce a new section of DNA inside healthy muscle cells. Once injected into muscle tissue, this strip of DNA codes for eCD4-IG protein that blocks the points where the HIV virus binds to both cellular receptors viz, CCR5 and CD4 leaving no point of entry. Thus enabling the cells to neutralize and provide sustained vaccine-like protection against HIV infection.
The research team led by Dr. Farzan including scientists from more than a dozen research institutions and both campuses of The Scripps Research Institute (TSRI) conducted their pre-clinical studies on four rhesus monkeys. In their study, monkeys were infected with a hybrid version of HIV, administering up to four times the amount of virus it took to infect a control group. They found that the protein protected the monkeys from every strain of HIV-1, HIV-2 and SIV (simian immunodeficiency virus) that has been isolated from humans or rhesus macaques, including the hardest-to-stop variants and it does so for at least eight months after injection.
The study builds upon previous discoveries by the Farzan laboratory, showing that proteins based on HIV-binding region of CCR5 can be used to prevent infection. Keeping this in mind Farzan and his team developed the new drug candidate as a direct mimic of the receptors by fusing together elements of both CCR5 & CD4 receptors to which HIV binds. Thus preventing the infection by excluding the avenues through which the virus tends to escape.
This therapy effectively eliminates the need for presentation of threat or viral peptides on the surface of cells by turning cells into factories that constantly spew out the artificial HIV-killers. Moreover it targets those areas of HIV which the virus struggles to change thus overcoming its rapidly mutating nature. Also the therapy in itself can prove as an alternative to antiretroviral drugs that are used for HIV treatment in terms of cost, side-effects as well as the difficult life-long regimen which the patients have to follow.
Although the long-term effects of this therapy are still unknown it is believed to have the potential to put HIV into sustained remission in chronically infected people. Nonetheless, the team plans to begin trials in patients who have HIV but are unable to take conventional drug therapies within the next year. The team also aims to test its efficacy as a vaccine, in people who don’t have the virus but are at high risk of infection, said Dr. Farzan.
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