French B A
Department of Medicine, Baylor College of Medicine, Houston, Texas.
Herz. 1993 Aug;18(4):222-9.
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.
在过去四年中，基本的重组技术（如分子克隆、测序、定点诱变、聚合酶链反应和转染）已被结合起来，产生了具有实验潜力的“第二代”重组DNA技术，而这种潜力在仅仅十年前几乎是无法想象的。本综述将聚焦于基因转移技术最近两项进展的起源及其在心血管方面的应用：同源重组基因靶向和直接体内基因转移。基因靶向技术源于转基因小鼠技术，但其独特之处在于能够精确破坏或“敲除”小鼠基因组中的特定基因。这不仅为功能问题提供了决定性的答案，还能产生人类遗传疾病的精确模型。体内基因转移可将遗传信息直接导入活组织。体内基因转移不仅通过提供一种简单直接的方法来分析完整动物体内的基因结构和功能，从而促进基础研究，而且还可能在治疗遗传和后天性疾病（如家族性高胆固醇血症和再狭窄）方面找到直接的临床应用。
