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Engineered Fusion Protein Opens Door for Safer Gene Therapy
A protein engineered by researchers at KU Leuven that combines proteins active in HIV and Moloney murine leukemia virus (MLV) replication may lead to safer, more effective retroviral gene therapy. KU Leuven is located in Flanders, the Dutch-speaking region of Belgium. Gene therapy involves inserting healthy genetic material into a diseased cell. Using a carrier derived from a retrovirus, the genetic material is smuggled into a human cell where, once inside, it integrates itself into the cell’s DNA. But gene therapy is not without risks. If integrated too near a carcinogenic gene, the newly introduced genetic material can also induce disease-causing mutations. In gene therapy, the delivery vehicle is not the retrovirus itself, but a viral vector: a derivative form of the retrovirus that retains its proteins but not its nucleic acid. One of the most widely used viral vectors is derived from MLV. But this particular virus-borne carrier is both a weapon and a risk. It can cure disease but, if integrates in the wrong place in a cell’s DNA, it can also cause leukemia. A separate protein, which plays a role in HIV, does not have that problem. It only integrates itself in ‘safe’ places in the host cell’s DNA. The researchers put one and two together to create a safer viral vector: “We developed a fused protein with the head of the protein that HIV uses and the tail of the protein that MLV uses,” Dr. Rik Gijsbers explains. Their work was reported online on October 31, 2013 in Cell Reports, and the researchers say their engineered retroviral vector works: “Our experiments with cell cultures show that in the presence of this protein, the viral vector always inscribes itself in a safe place, just as it does in the HIV virus,” says Dr. Gijsbers.