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Genetic trick adapted from viruses makes gene therapy vectors more versatile

A genetic trick used by viruses to replicate themselves has been adapted for laboratory use to build complex protein structures required by immune system cells, according to investigators at St. Jude Children's Research Hospital.

This approach could also be used to develop new gene therapy vectors in cases when cells must be modified to make high levels of different proteins. A vector is a DNA molecule used to ferry specific genes into cells in order to give those cells the ability to make particular proteins.

A report on this work appears in the May 2004 issue of Nature Biotechnology.

The achievement gives researchers a powerful tool for studying the roles of complex proteins in living cells. The study also showed that this technique can reliably produce therapeutically useful amounts of multiple proteins. Some cellular proteins must be present in many copies in order to work efficiently. Because it only borrows a genetic trick from viruses but does not cause a real infection, the technique may increase the usefulness of current gene therapy vectors. Specifically, the technique would permit scientists either to restore complex protein structures that are missing in certain cells or make multiple proteins that act together as potent drugs against cancer and other diseases.

The technique is based on a genetic trick, called a self-cleaving 2A peptide, which is used by some viruses to produce multiple proteins from a single length of DNA; i.e., a single, long protein is produced that automatically breaks into multiple, distinct proteins.

St. Jude researchers used genetically modified mouse immune system cells called T lymphocytes to test the efficiency of this technique in making the CD3 complex, which is part of the T cell receptor, a large protein lodged in the cell's membrane. The receptor allows T cells to "sense" targets that the cells are programmed to destroy. Without the CD3 complex, the T cell receptor is incomplete and canno
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Contact: Bonnie Cameron
bonnie.cameron@stjude.org
901-495-4815
St. Jude Children's Research Hospital
5-Apr-2004


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