Genomics Integrated Systems Transgenesis (GENISYST) for gain-of-function disease modelling in Göttingen Minipigs.

Abstract Gottingen Minipigs show several anatomical, physiological, and pathogenetical similarities to humans and serve an important role in translational studies for example as large animal models of disease. In recent years, the number of transgenic Gottingen Minipigs models has increased, as advanced genetic techniques simplify the generation of animals with precisely tailored modifications. These modifications are designed to replicate genetic alterations responsible for human disease. In addition to serving as valuable large animal disease models, transgenic Gottingen Minipigs are also considered promising donors for xenotransplantation. Current technologies for generation of transgenic minipigs demand a long development and production time of typically 2–3 years. To overcome this limitation and expand the use of Gottingen Minipigs for disease modelling and drug testing, we developed the GENISYST (Gene-Disease Integrative Systems Transgenesis) technology platform for rapid and efficient generation of minipigs based transgenic disease models. As proof of concept, we report the successful generation of transgenic minipigs expressing green fluorescent protein (GFP) in multiple disease-relevant tissues including liver, heart, kidney, lungs, and the central nervous system (CNS). Our data demonstrates the feasibility, efficiency, and utility of GENISYST for rapid one-step generation of transgenic minipigs for human disease modelling in drug discovery and development.