"This allows us to expand the types of cells that can be treated with genetic therapy, because we get a virus that can infect those cells that the alphavirus would infect rather than the ones that the native retrovirus would infect," he says. "Retroviruses, in their natural state, infect only a few specific types of cells. The HIV virus, for example, will infect essentially only macrophages and T-cells." Retroviruses are often used in gene transfer because once inside a cell, they can copy part of their DNA into the genetic code of the host cell. For gene therapy, the harmful parts of the virus' genetic code are replaced with genes intended to treat disease, so patients can be treated without suffering any harmful effects from the virus. The cell will then produce new cells that contain the therapeutic gene. The first commonly used pseudotyped retrovirus system called VSV-G because it was developed using the glycoprotein coat of a vesicular stomatis virus currently is used in some gene therapy processes. "Both systems can infect mammalian and insect cells, but our new system presents several advantages over VSV-G in gene therapy and gene transfer," Sanders says. "For example, VSV-G is toxic, both to cells that are being infected and to cells that are producing the virus. We have seen no signs of toxicity using our system. That should allow these particular viruses to be the virus of choice for gene transfer mediated by retroviruses."
Experiments in cell cultures also indicate the new system can transfer genes in a permanent, dependable fashion, Sanders says. "One problem with some of the current carrier systems, including VSV-G, is that gene transfer with them can be transient."
Another advantage is that the cell lines developed to produce these carrier viruses can make the viruses indefinitely, Sanders says.
"You cannot do that with the VSV-G," he says. "O
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Contact: Susan Gaidos
sgaidos@purdue.edu
765-494-2081
Purdue University
20-Mar-2001