The methodologies and application potential of genetically modified farm animals

The first transgenic livestock were produced in the mid-1980s by microinjection of foreign DNA into zygotic pronuclei and remained the method of choice for more than 15 years, when it was gradually replaced by functional somatic cell nuclear transfer (SCNT) protocols. Recently, molecular scissors, including Zinc Finger Nucleases (ZFN), Transcription Activator-like Effector Nucleases (TALEN) and the CRISPR/Cas (Clustered Regularly Interspaced Short Palindromic Repeats) system have been successfully applied in the livestock species and were shown to allow precise modifications of the genome. Although the efficiency of transgenic animal production by microinjection technology was low, many animals with agriculturally important transgenic traits were produced by this method, including improved carcass composition, lactational performance, wool production, enhanced disease resistance and reduced environmental impact. However, none of the transgenic livestock with enhanced production traits has been accepted for commercial use, with the exception of the AquaAdvantage Atlantic salmon from the company Aquabounty. In contrast, at least three recombinant pharmaceutical proteins produced from the mammary gland of transgenic animals were approved by the supervisory agencies in Europe and North America. Moreover, numerous transgenic pig models for important human diseases have been produced and pigs with multiple genetic modifications have contributed to significant progress in xenotransplantation research. The use of DNA nucleases will pave the way to precision breeding concepts in livestock.