It all started with the “Berlin Patient” in 2007. Timothy
Brown was cured of HIV when given the stem cells of another patient who was
naturally immune to the disease. When this happened two companies, Sangoma and
Calimmune, took the opportunity to attempt to recreate the natural immunity to
HIV in a lab. This natural immunity occurs because of a gene mutation on the
CCR5 gene which is located on CD4 T-cells. When this gene is disable HIV cannot
attack the T-cells.
Sangamo was the first to attempt the recreation in 2009.
Lead by Carl June from the University of Pennsylvania, a team of researchers
and doctors removed CD4 T-cells from patients with HIV. The study then focused
on disabling the CCR5 gene alleles and then returning the modified cells to the
patient. It was stated that this did no harm to the patients and the altered
genes had a half-life of 48 day, which is expected because “…T-cells are not
permanent residents of the body”. In fact, several of the patients in this
study even exhibited a decline in their HIV levels.
The next company to attempt to recreate the natural immunity
to HIV is Calimmune. In 2013 a team led by David Baltimore and Irvin Chen decided
to take a different approach to solve the task at hand. Instead of focusing
their work on T-cells, they decided to take advantage of blood stem cells. This
approach is different because blood stem cells, unlike T-cells, are permanent
residents in the body. During this study patients were “given back both their
own T cells, and longer-lived HSCs [blood stem cells], both with the CCR5 gene
disabled using hairpin RNAs delivered by a lentivirus.” By doing this they hope
that these blood stem cells can continue to produce T-cells with disabled CCR5
gene alleles throughout a patient’s lifetime.
Despite the fact that neither of these studies have
conclusive clinical trials yet, Harvard University has decided to be next in
the search for a cure for HIV. Their approach will include new CRISPR/Cas
technology which has already proven effective in mice. It was stated that
Harvard may even apply for clinical trial approval in five years.
Related Article: http://www.nejm.org/doi/full/10.1056/NEJMoa1300662
