Gene transfer and cardiovascular disorders

Within the past four years, basic recombinant techniques (such as molecular cloning, sequencing, site-directed mutagenesis, PCR, and transfection) have been combined to yield a "second generation" of recombinant DNA technology with experimental potential which could barely have been envisioned only a decade ago. This review will focus upon the genesis and cardiovascular application of two recent developments in gene transfer technology: gene targeting by homologous recombination and direct in vivo gene transfer. Gene targeting evolved from transgenic mouse technology but is distinguished by its ability to precisely disrupt or "knock-out" specific genes in the murine genome. This not only provides decisive answers to functional questions, but also produces accurate models of human genetic disorders. In vivo gene transfer provides for the direct introduction of genetic information into living tissues. In vivo gene transfer not only facilitates basic research by providing a simple and direct way to analyze gene structure and function in intact animals, but may also find direct clinical application in the treatment of genetic and acquired disorders such as familial hypercholesterolemia and restenosis.