Word: retroviruses
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Knowing he needed help, he began collaborating with retrovirus researcher Eli Gilboa and Dr. Michael Blaese, an NIH pediatrician and expert in immunology. Over the next few years, Anderson submitted proposals for human gene-therapy trials to the NIH's Recombinant DNA Advisory Committee (RAC), which must approve such tests...
...hardest part of all these efforts is getting the right genes into the cells that need them. Generally, the genes must be carried by some sort of delivery vehicle, which scientists call a vector. For its vector, Anderson's team used an infectious agent known as a retrovirus -- a specialized virus containing RNA (a single-strand cousin of DNA) that has a knack for finding its way to a cell's genome and making itself at home. Retroviruses can be dangerous (HIV is the most notorious), but scientists have ways of altering them so that they don't cause disease...
Anderson, then at the NIH, with colleagues Dr. R. Michael Blaese and Dr. Kenneth Culver, extracted T cells from the little girl's blood and exposed them to a mouse-leukemia retrovirus that had been rendered harmless and endowed with a normal ADA gene. Invading the T cell, the retrovirus acted as a vector, depositing its genetic material, including the ADA gene, in the cell nucleus. After the re-engineered T cells were cultured, a process that produced billions of them, they were infused back into the child's bloodstream, where their new gene began producing the ADA enzyme...
...Like the retrovirus used by Anderson, Rosenberg's delivery system has been made harmless and endowed by recombinant DNA techniques with a human gene. But this gene codes for tumor necrosis factor, a naturally occurring compound that attacks cancer cells. The altered viruses insert themselves and their piggyback gene into the genetic material of the TILs, which are then injected back into the bloodstream of the melanoma patients. If everything goes as planned, the activated TILs will home in on the tumors like guided missiles, attacking the cancerous cells and at the same time releasing the antitumor factor to help...
Undaunted, researchers are refining their techniques in experiments with mice, and Mulligan believes that the first human-gene-therapy experiments could occur in the next three years. Looking further ahead, other scientists are experimenting with a kind of genetic microsurgery that bypasses the retrovirus, mechanically inserting genes directly into the cell nucleus...