Refining genome editing in livestock

该项目旨在完善基因工程(GE)技术，从而为从事生物科学的学术和商业部门提供更好的工具。通用电气家畜最早是在大约25年前生产的。从那时起，所使用的技术得到了改进。然而，它们仍然效率低下，缺乏精确度。生产转基因家畜的理想技术将是一种能够有效地对受精卵进行精确工程的技术。令人兴奋的是，这一点现在正在出现--我们现在可以用设计好的杂交内切酶改造受精卵，而不会留下‘转基因’的标记。从本质上讲，这些酶的功能就像是一把分子剪刀，精确地将基因组切割到你想要切割的位置。这项新兴技术基于基因组编辑，例如ZFN和TALEN。我们最近已经证明，TALEN和ZFN直接注射到猪受精卵中都可以产生活的基因组编辑的猪。我们现在的目标是改进方法，论证转基因技术在家畜中提高效率是可能的，重点放在以下四个目标上，这些目标建立在我们初步数据的基础上：提高效率，减少变异性，通过发展改变特定DNA序列的能力来扩大应用范围，并在反刍动物中演示该方法。如果将这项技术应用于农业部门和生物技术部门，就有可能产生变革性的影响。

This project aims to refine genetic engineering (GE) technology thus providing better tools for both the academic and commercial sectors working in the biosciences. GE livestock were first produced about 25 years ago. Since then improvements in the technology used have been developed. However, they remain inefficient and lack precision. The ideal technology for producing GE livestock would be one that enable the efficient a precise engineering of the zygote. Excitingly this is now emerging - we can now engineer the zygote with designer hybrid endonucleases that do not leave a 'transgenic' mark. In essence these enzymes function as molecular scissors cutting the genome precisely where you want it to be cut. This emerging technology is based on genome editors, examples of which include ZFN and TALEN. We have recently demonstrated that both TALEN and ZFN injected directly into pig zygotes can produce live genome edited pigs. We now aim to refine the method arguing that efficiency improvements are possible for GE technology in livestock, focussing on the following four objectives which build on our preliminary data: increase efficiency, reducing variability, broadening application through developing ability to change specific DNA sequences, and demonstrating the method in ruminants. This technology has the potential to be transformative in its impact if applied in the agricultural and biotechnology sectors.