LARGE SCALE GENE TARGETING FOR FUNCTIONAL GENOMICS

我们建议开发技术， 在小鼠中的灭活速度比目前快10到50倍 可能 这种“基因敲除”转基因小鼠对于 了解生物体的基因功能和疾病过程 水平 而不是传统的方法，依赖于限制 酶通过重组DNA程序构建靶向载体， 利用重组机制的新质粒和方法 快速组装靶向载体的细菌将被开发。 这些向量将被更精确地构建，并且至少是 比常规靶向更有效地进行同源重组 向量。 建议的商业应用 高效、大规模基因打靶技术的发展 将加速基因发现和基因功能分析， 为了更快地发展人类疾病的诊断和治疗， 遗传病 有价值的疾病动物模型也将是 生成的.

We propose to develop technologies for making targeted gene inactivations in mice ten to fifty fold faster than is currently possible. Such "knockout" transgenic mice are critical for understanding gene function and disease processes at the organismal level. Instead of conventional approaches that rely on restriction enzymes to construct targeting vectors by recombinant DNA procedures, novel plasmids and methods for harnessing the recombinational machinery of bacteria to rapidly assemble targeting vectors will be developed. These vectors will be more precisely constructed and will be at least as efficient at homologous recombination than conventional targeting vectors. PROPOSED COMMERCIAL APPLICATION The development of efficient, large-scale gene targeting technologies will accelerate gene discovery and gene functional analysis providing for more rapid development of diagnostics and therapeutics for human genetic diseases. Valuable animal models for diseases will also be generated.