Stem cell genome edited to create HIV-resistant immune cells

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'.