"This is elegant scientific research that needs lots of further study," Dr. Anthony Fauci
told Windy City Times about yesterday's (March 5, 2014) blockbuster news that investigators had initial success with thwarting HIV through an intentional genetic altering of human cells.
Funded by the National Institutes of Health, a study with 12 HIV-infected individuals indicates it is possible to curb HIV disease by removing key cells from infected individuals and genetically modifying the cells to resist HIV infection and then returning them to those people.
The novel approach eventually might help people control the virus without drugs. "This type of research has been tried with cancer as well," Fauci explains. He stresses that the success of this study is exciting but only a start on answering lots of questions on how this genetic alteration of cells can be molded into an effective treatment strategy.
How does the genetic modification process work?
We all have a protein called CCR5. The protein is a "doorway" through which HIV infects cells. The doorway is on each CD4+ T cell, the cells that help us fight infection.
Some people have a naturally occurring genetic version of CCR5 that does not allow HIV to enter CD4+ T cells. Through a safe, genetic modification process, scientists altered the CCR5 protein to mimic the naturally occurring version in people who fight off or more slowly experience HIV infection. Modification of the CCR5 protein does not allow HIV to infect cells.
Scientists collected CD4+ T cells from each of 12 HIV-infected volunteers whose virus is controlled by HIV medicines. These collected 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 that made the CCR5 receptors unable to be infected by HIV. Then, the cells were stimulated to multiply, and each patient received an infusion of 10 billion of their own CD4+ T-cells. After the infusion, patients had roughly one-fifth of their CCR5 genes now mutated.
"We call the modified cells 'edited' cells because we have changed them," Fauci explains.
Four weeks later, one-half of the 12 patients stopped taking their HIV medicines for 8 to 12 weeks as a planned step in the study. Investigators found that the experimental treatment was generally safe, and that the genetically modified cells appeared to be protected from HIV infection. In one volunteer who naturally had the desired mutation in half of his CCR5 genes, HIV replication was controlled during the entire 12-week time period when no HIV medicines were taken.
Where does the research go from here?
Future research will include evaluating the experimental treatment in more volunteers. Investigators will also have to figure out how to have an infected individual "keep" genetically modified cells in the body to inhibit HIV infection. It is not known, for example, if one infusion of mutated cells is sufficient or how long the desired cell alteration may last or if altered infusions must occur over time or on a regular basis.
"We do not know if patients need partial or complete replacement of all CD4 cells or how long partial or complete cell replacement with modified cells may last," Fauci cautions.
To volunteer for the study, ask your HIV doctor about enrollment through NIH.