March 15, 2006
Fat Nanoparticle Gene Therapy Against Cancer

In theory gene therapy ought to be the ideal way to cure cancer. Cancer develops as a result of a series of mutations that make cells divide and spread out of control. Gene therapies that correct the mutations ought to stop cancer. But delivery mechanisms that can reach the vast bulk of cancer cells are hard to find. Also, adding back in correct p53 and other mutated genes might mess up normal cells by causing them to have too many copies of those genes. University of Texas M.D. Anderson Cancer Center researchers haven't solved all those problems but they are testing nanoparticles as a delivery mechanism for gene therapy against cancer.

Nanoparticles may offer an answer. The newest strategy to emerge out of Roth's lab is a blob of lipid smaller than a cell or nanoscale, a type of fat that holds therapeutic genes. Developed by Nancy Templeton, Ph.D., of Baylor College of Medicine, the special nanoparticle is of a size that is easily absorbed into cells. "Dr. Templeton hit upon a nanoparticle that had a very efficient transfer into cells," says Charles Lu, M.D., an assistant professor in the Department of Thoracic/Head and Neck Medical Oncology and co-investigator.

The nanoparticles carry a new payload as well. They encase, like shrink wrap, a normal p53 gene as well as a second gene, FUS1, which is frequently altered or missing early in the development of many solid tumors.

So far, nine patients with metastatic lung cancer have been tested with the therapy in a phase I trial headed by Lu. In all, 30 patients are expected to be enrolled. The trial is a "dose escalation" study, which looks for side effects as doses of the drug are increased. "So far, there have been no significant safety issues," says Lu.

The study is the first to test nanoparticle therapy in treating human cancer, according to Lu. "No one before has tried intravenous injections using nanoparticles to replace genes that are lost or defective. This non-viral aspect is very different in gene therapy. It may offer major benefits because nanoparticles are non-infectious. They are inert; there are no infection risks to use bubbles of fat.

"If successful - and that is a very big if - nanoparticles may prove to be a way to deliver gene therapy systemically, potentially treating metastatic disease in multiple cancer sites," says Lu.

What isn't known yet, however, is how often normal cells will absorb the drug and what effect that will cause. Preclinical study seems to show that tumor cells preferentially take up the bubbles - and researchers are pleased with that finding, although they don't know why it happens - but healthy cells can also sop up the new genes. "It may not have too much of an effect on normal cells because they already have these beneficial genes, but we just don't know yet," says Lu.

An excess of p53 activity in normal cells would accelerate aging by causing too many cells to kill themselves through a process called apoptosis. But if you are faced with terminal cancer the risk of accelerated aging seems like the smaller immediate threat.

The full article outlines other gene therapy approaches M.D. Anderson reseachers are pursuing against cancer.

Successful development of gene therapy delivery mechanisms against cancer would open up many other diseases for gene therapy treatments. Gene therapy has failed to deliver on its early promise. We know the genetic causes of hundreds of diseases. So we know what needs reprogramming to cure many diseases. But we lack the ability to easily upload new genetic programs into cells. Once we have much better ways to do that the continued accumulation of knowledge about harmful genetic mutations will finally find ways to be used in therapies.

Share |      Randall Parker, 2006 March 15 09:30 PM  Biotech Gene Therapy

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