SOFTWARE UPDATE: Gene Editing Could Rescue AIDS Patients
HIV Gains Foothold: The human immunodeficiency virus, HIV, gains entry into immune T cells by initially binding to the cell surface receptor protein CD4 and then recruiting a co-receptor, usually CCR5. Infected T cells eventually die and the patient becomes susceptible to other infections, described as acquired immunodeficiency syndrome or AIDS.
As Luck Would Have It: About ~700 years ago, a chance mutation in the CCR5 gene appeared that inactivated the receptor. This mutation, CCR5-Δ32, has a slight negative fitness effect because CCR5 is one of many chemokine receptors important in the inflammatory immune response. The mutation should have dwindled or disappeared. Instead, the mutation underwent intense positive selection, now prevalent in ~10% of the European population. Modeling studies suggest that the mutation helped fight off small pox virus, conferring an unexpected survival benefit. Today, it provides resistance to HIV: one copy of the mutation delays AIDS onset ~ 2 years, while 2 copies confers resistance to the common HIV-1 R5 strain.
The Berlin Patient: A famous case of “natural gene therapy” involved Timothy Ray Brown who was being treated for HIV infection in the mid-nineties. Brown then developed leukemia in 2006 and his condition deteriorated. He received a stem cell transplant from a German donor whose CCR5 genes carried the resistant mutation. Not only did the treatment cure Brown’s leukemia, it also eliminated the HIV infection (http://en.wikipedia.org/wiki/The_Berlin_Patient).
Gene Editing: Recent efforts are designed to be more accessible for AIDS patients. The idea is to remove T cells from the patient, manipulate the CCR5 gene to insert mutation, then re-introduce the modified T cells back into the patient. A small-size feasibility and safety study was reported this week (http://goo.gl/TlRBrG) involving 12 patients: 6 received modified T cells and were taken off anti-retroviral therapy for 4 weeks. The results were promising! T cell counts increased in the treatment group, and the modified cells outlasted the unmodified cells by 7-fold. The paper is behind a paywall, so please ask if you have questions! The news story is here: http://goo.gl/j5jkws
Image shows an immune T cell (yellow) in the lower right, budding off particles of HIV (green) seen in a colored transmission electron micrograph from http://www.sciencephoto.com/media/549097/. To the upper left, is a molecule of CCR5 (yellow) embedded in the cell membrane (grey lipid) from Wikimedia (http://goo.gl/svUNsE).