Doran Timothy J, Cooper Caitlin A, Jenkins Kristie A, Tizard Mark L V
Australian Animal Health Laboratory, CSIRO Health and Biosecurity, Private Bag 24, Geelong, VIC, 3220, Australia.
Transgenic Res. 2016 Jun;25(3):307-19. doi: 10.1007/s11248-016-9926-8. Epub 2016 Jan 28.
This review provides an historic perspective of the key steps from those reported at the 1st Transgenic Animal Research Conference in 1997 through to the very latest developments in avian transgenesis. Eighteen years later, on the occasion of the 10th conference in this series, we have seen breakthrough advances in the use of viral vectors and transposons to transform the germline via the direct manipulation of the chicken embryo, through to the establishment of PGC cultures allowing in vitro modification, expansion into populations to analyse the genetic modifications and then injection of these cells into embryos to create germline chimeras. We have now reached an unprecedented time in the history of chicken transgenic research where we have the technology to introduce precise, targeted modifications into the chicken genome, ranging from; new transgenes that provide improved phenotypes such as increased resilience to economically important diseases; the targeted disruption of immunoglobulin genes and replacement with human sequences to generate transgenic chickens that express "humanised" antibodies for biopharming; and the deletion of specific nucleotides to generate targeted gene knockout chickens for functional genomics. The impact of these advances is set to be realised through applications in chickens, and other bird species as models in scientific research, for novel biotechnology and to protect and improve agricultural productivity.
本综述提供了从1997年第一届转基因动物研究会议报道的关键步骤到禽类转基因最新进展的历史视角。十八年后,在本系列第十届会议之际,我们见证了在利用病毒载体和转座子通过直接操纵鸡胚来转化生殖系方面取得的突破性进展,直至建立PGC培养物,实现体外修饰、扩增成群体以分析基因修饰,然后将这些细胞注射到胚胎中以创建生殖系嵌合体。我们现在处于鸡转基因研究历史上前所未有的时期,拥有将精确的靶向修饰引入鸡基因组的技术,包括:提供改善表型(如对经济上重要疾病的抵抗力增强)的新转基因;免疫球蛋白基因的靶向破坏并用人类序列替代,以产生表达用于生物制药的“人源化”抗体的转基因鸡;以及删除特定核苷酸以产生用于功能基因组学的靶向基因敲除鸡。这些进展的影响将通过在鸡和其他鸟类物种作为科研模型、新型生物技术以及保护和提高农业生产力方面的应用来实现。