St. Louis, Oct. 21, 1998 -- Scientists often use the genetic material of viruses to smuggle foreign genes into cells. But such vectors frequently kill the cells they enter, limiting their long-term utility. For the first time, researchers at Washington University School of Medicine in St. Louis have devised a way to create harmless vectors from a harmful virus. In a paper in the Oct. 27 issue of Proceedings of the National Academy of Sciences, they show that the vectors are efficient couriers of genes.
"A similar strategy might work for modifying other cytotoxic viruses that are being used as gene vectors," says Charles M. Rice, Ph.D., professor of molecular microbiology and head of the research team. Postdoctoral fellow Eugene V. Agapov, M.D., Ph.D., and Ilya Frolov, Ph.D., research assistant professor of molecular microbiology, were the paper's lead authors.
By transferring foreign genes into cultured cells, scientists can study the regulation and functions of those genes under controlled conditions. They also can alter the activities of cells, to compensate for a defective gene, for example. Commenting on Rice's paper in an accompanying article, Peter Palese, Ph.D., of Mount Sinai School of Medicine, says that the "long-term expression of foreign proteins in a noncytotoxic manner may blow new wind into the sails of our gene therapy enterprise." This new type of vector might eventually be used to deliver DNA vaccines, he also suggests.
Rice and colleagues worked with Sindbis virus, which produces fever, headache and musculoskeletal symptoms. The virus's genetic material is a single strand of RNA, which Washington University research groups engineered into a gene vector in 1989.
To obtain vectors that will not kill cells, the researchers first
inserted an extra gene into modified pieces of Sindbis RNA. The gene coded for a
protein that inactivates puromycin
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Contact: Linda Sage
sage@medicine.WUSTL.edu
314-286-0119
Washington University School of Medicine
27-Oct-1998