Gene therapy involves either the delivery of whole active genes (gene transfer) or the blockade of native gene expres¬sion by transfection of cells with short chains of nucleic acids (oligonucleotides). These short, single-stranded DNA molecules are used as drugs to target the inactivation of mRNA- or DNA-binding proteins.
Manipulation of gene activity or gene expression is achieved by introducing foreign DNA into target cells where subsequently it is expressed in a process known as transduction or transfection (see Fig. 1). Systems include recombinant viral vectors that permit relatively competent insertion of genetic information and oligonucleotides that are used to modify native gene expression. Gene blockade may also be achieved by the use of ribozymes, segments of rRNA that can act as enzymes to destroy certain sequences of target mRNA. A third type of gene blockade involves the use of gene regulatory proteins known as transcription factors, which regulate gene expression by binding to chromosomal DNA. This process activates an adjacent gene. Synthetic DNA decoys prevent binding of transcrip¬tion factors to the promoter site of many genes involved in cell proliferation. This process inhibits cell cycle progres¬sion, potentially leading to inhibition of neointimal hyper-plasia and may cause reduction in stenosis of venous bypass grafts.

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