New Gene Therapy Blocks HIV Infection

Sometimes, the smallest alterations lead to the largest breakthroughs. In what appears to be a promising step forward in the war against AIDS, researchers have genetically engineered patients' vital immune system cells to make them resistant to HIV infection, the Philadelphia Inquirer reported. Scientists did this by taking immune cells from nine HIV-positive patients' own blood and then cutting out a single gene using a tool called "zinc fingers" – an atom of zinc that binds to two loops of proteins.  It was developed by Sangamo BioSciences of Richmond, California, which funds human testing of engineered T cells. Zinc fingers can recognize sequences of DNA, and so by attaching a protein that cuts DNA, the zinc fingers become, essentially, "scissors" that can work on a molecular level and are able to cut, delete or insert genes. After cutting out the gene, the engineered cells were put back in the patients, and scientists observed that they were no longer able to make a receptor that HIV requires to enter the cell.  This blocked the virus from spreading. The cells in all nine of the patients remained HIV-free throughout the duration of the study.  Not only that, but the cells multiplied dramatically in eight of the patients and accounted for about 6 percent of their total immune cells (T cells). There were no serious side effects besides occasional headaches, chills and fever. Gene therapy expert Carl June presented the data at an AIDS conference Wednesday in Boston.  He believes this therapy shows the most promise of any experimental therapy yet tested. "It's a big accomplishment because this is the first successful attempt at genetic editing," June said. "It gives us an essential tool." Scientists have never before had access to this level of precision.  Previously, gene therapy centered around viruses that inserted genes randomly into cell DNA. However, patients only have partial immunity by producing HIV-resistant T cells because there are many other types of immune cells in the human body.  The question still remains over whether it is possible or not to achieve total immunity – in other words, cure HIV – by altering the entire immune system. For one man, this wild possibility has already become reality.  In 2009, an HIV-positive man in Germany received a stem-cell transplant from a donor who was naturally resistant to HIV.  The donor had a gene mutation in which his T cells could not make the receptor HIV needed. "You can inherit one copy or two copies of the mutation," June said. "About 1 percent of people have two copies and are completely resistant to HIV." Researchers have already shown they can cure HIV in mice by deleting the receptor-making gene from blood stem cells, then transplanting these cells. However, this treatment may be unfeasible for humans, because it requires destroying the entire blood immune system with toxic drugs and then infusing stem cells over the course of several weeks to rebuild the system.  For a patient with an already weak immune system, the treatment could be lethal. Another concern arises over the source of the stem cells.  A patient's own stem cells are already infected with HIV.  However, using donated stem cells runs the risk of rejection. Click here to read more from the Philadelpia Inquirer.