LARGE SCALE GENE TARGETING FOR FUNCTIONAL GENOMICS

我们建议开发制造靶向基因的技术 小鼠的灭活速度比目前快10到50倍 有可能。这种“敲除”的转基因小鼠对 在生物体中了解基因功能和疾病过程 水平。而不是依赖于限制的传统方法 酶通过重组DNA程序构建靶向载体， 用于利用重组机制的新型质粒和方法 将开发快速组装靶向载体的细菌。 这些向量将被更精确地构建，并将至少像 比传统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，提供 为了人类诊断学和治疗学的更快发展 遗传病。有价值的疾病动物模型也将是 已生成。

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.