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Stem cell genome edited to create HIV-resistant immune cells

16 June 2014

By Rhys Baker

Appeared in BioNews 758

Cells have been made resistant to HIV after researchers rewrote their genome to contain a gene variant linked to immunity against the virus.

The team at the University of California, San Francisco, led by Professor Yuet Wai Kan, edited the genome of induced pluripotent stem cells (iPSCs) to exactly mimic a naturally occurring mutation that provides resistance to HIV infection. Although they hope this can be developed into a HIV cure, this is likely to be some way off. As Professor Kan told New Scientist: 'One of the problems is converting iPSCs into a type of cell that is transplantable'.

HIV infects a person's immune system by latching on to a protein called CCR5, found in white blood cells. Around one percent of people of European descent are resistant to HIV infection because they have a mutated form of CCR5 that the virus cannot lock on to. The researchers introduced this mutation artificially into the genome of iPS cells, exactly mimicking the natural mutation.

This is not the first time the CCR5 gene has been targeted. Timothy Ray Brown, known as the Berlin Patient, receiveda stem cell transplant from an HIV-resistant bone marrow donor, functionally curing him of the disease. However, so few people carry this mutation naturally that finding a compatible donor for each HIV patient would be impossible.

Other studies have used genome editing to directly modify the CCR5 gene of HIV-infected patients. This method requires repeated transplants, something that is considered undesirable. If Professor Kan is successful in creating transplantable, HIV-resistant stem cells that can develop into all types of blood cells, treatment should require a single transplant. Crucially, they would all possess the HIV-resistant CCR5 mutation, making it impossible for HIV to lock on and infiltrate any white blood cells.

Dr Louis Picker from Oregon Health and Science University told Wired.co.uk: 'Keeping in mind that bone marrow transplant is not likely to be an option for treating the vast majority of HIV positive subjects on effective anti-retroviral therapy, [this] technology is no question a break-through, but whether this application will have wide impact is difficult to predict at this time'.

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