Scientists today report
initial results from humans on the safety and tolerability of a novel
strategy to curb HIV disease by removing key cells from HIV-infected
individuals,
genetically modifying the cells to resist HIV infection and returning
them to those people. The basic and pre-clinical research on this
strategy, which eventually might help people control the virus without
drugs, was funded by the National Institute of Allergy
and Infectious Diseases (NIAID), part of the National Institutes of
Health. The Phase I clinical trial was funded by Sangamo BioSciences and
was led by NIAID grantee Carl H. June, M.D., with co-investigators
Bruce L. Levine, Ph.D., and Pablo Tebas, M.D., all
of the Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
The trial built on the
observation that people who naturally have a genetic modification in a
protein called CCR5 are resistant to HIV infection, and when infected
with HIV,
progress to AIDS more slowly. CCR5 is a cell-surface molecule, or
receptor, that most HIV variants must use to enter their primary target:
the CD4+ T
cell. In the trial, CD4+ T-cells
were collected from each of 12 HIV-infected volunteers
whose virus was controlled by anti-HIV therapy. These cells were then
treated in the laboratory with molecular tools called zinc-finger
nucleases (ZFNs). The ZFNs were designed to snip the DNA within the gene
that codes for the CCR5 receptor. This process
introduced a genetic mutation rendering CCR5 receptors non-functional.
Subsequently, the cells were stimulated to multiply, and each patient
received an infusion of 10 billion of their own CD4+ T-cells,
with roughly a fifth of the CCR5 genes now mutated.