Transgenesis

Abstract

The first transgenic livestock was produced in 1985 by microinjection of foreign DNA into zygotic pronuclei. This was the method of choice for more than 20 years, but more efficient protocols are now available based on somatic cell nuclear transfer (SCNT), which permits targeted genetic modifications. Although the efficiency of transgenic animal production by microinjection technology is low, many animals with agriculturally important transgenic traits were produced by this method. Typical applications included improved carcass composition, lactational performance, wool production, enhanced disease resistance, and reduced environmental impact. Transgenic animal production for biomedical applications has found broad acceptance. In 2006, the European Medicines Agency approved commercialization of the first recombinant protein drug produced by transgenic livestock. This recombinant antithrombin III, produced in the mammary gland of transgenic goats, was launched as ATryn ® for prophylactic treatment of patients with congenital antithrombin deficiency. Pigs expressing human immunomodulatory genes have contributed to significant progress in xenotransplantation research with survival periods of nonhuman primates receiving transgenic porcine hearts or kidneys approaching 6 months. The production of transgenic farm animals is labor and cost intensive, as it requires advanced techniques in molecular biology, cell culture, reproductive biology, and biochemistry. Here, we summarize the current status of transgenic animal production with emphasis on large domesticated animal species; transgenesis by microinjection of recombinant DNA into the pronuclei of freshly fertilized oocytes (zygotes); and transgenesis by somatic cell transduction followed by nuclear transfer (SCNT). We also briefly describe several emerging gene-transfer methods that may bring significant improvements in the efficiency, precision, and safety of gene transfer. This contribution is an extension of previous reviews by the same authors, which include the original references for the interested reader.