Friday, March 7, 2014

Genetic modifications of CD4 T cells protect HIV infected individuals

Genetic modifications of CD4 T cells protect HIV infected individuals even after discontinuation of antiretroviral drug therapy.

Genetic modification of CD4 cells could be a life saving therapy for HIV can protect individual from developing disease in to AIDS. Scientists at National Institute of Allergy and Infectious Diseases (NIAID) Perelman School of Medicine at the University of Pennsylvania, Philadelphia have developed a technique with which an HIV virus can be completely inhibited from proliferation and HIV can’t infect new CD4 cells even after discontinuation of antiretroviral drugs.

HIV infected person have to take medication throughout the life, or HIV may relapse after discontinuation of drug treatment. Same is the true for the baby which was declared HIV free few days back a 9 month old newly born baby born to HIV positive mother was successfully treated with drugs and found HIV negative after rigorous treatment with antiretroviral drugs treatment but it could not be assured that the baby will never relapse HIV infection again after discontinuation of drugs. Genetic modification of CD4 T cell CCR5 can protect a individual even after discontinuation of drug therapy.

HIV virus attack on CD4 T cells as these cells have a receptor CD4 and make entry in to human cell and make use of these cells for its proliferation and multiplication, HIV enters CD4 T cells make use of cellular mechanism and multiply in number. There is a receptor CCR5 over CD4 T cells which is important for entry of HIV inside CD4 cells.

Scientists at NIAID in a Phase I clinical trial modified CD4+ T cell CCR5 receptor genetically so that it can’t be used as entry port by HIV for gaining entry in to human CD4 cells. This involved treatment of isolated CD4 cells from volunteer’s blood sample and treating them with zinc-finger nucleases (ZFNs), which resulted in to alteration in gene of CD4 cells which do not code for complete CCR5 receptor thereby making these cells resistance for entry of HIV in them. These cells were proliferated in laboratory and injected in to HIV positive individuals and drug treatment was stopped after four weeks after injection of genetically modified CD4 t cells.

12 HIV positive volunteers who were on rigorous antiretroviral drug therapy to keep HIV virus count under control participated in a clinical trial, about 10 billion genetically modified CD4 cells of their own were injected in them.

After 8 to 12 weeks it is found that these genetically modified cells protected them from HIV newly infused cells proliferated in these individuals and found to be resistant to HIV virus, further clinical trials are being conducted to evaluate the reproducibility of result in more number of subjects.
Role of CD4 receptor and CCR5 receptor in the process of entry of HIV in to  CD4 T cell 

Phase I clinical trial was funded by Sangamo BioSciences And led by grantee Carl H. June, M.D., Bruce L. Levine, Ph.D., Pablo Tebas, M.D Perelman School of Medicine at the University of Pennsylvania, Philadelphia.

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