Using a virus related to HIV as a vector, a group of German scientists has developed a highly efficient method for creating transgenic pigs, thus overcoming a major obstacle to the use of these animals not only as research models, but also for the production of therapeutic proteins and organs for xenotransplantation.

Traditional transgenesis by microinjection of DNA into the pronuclei of fertilized eggs is extremely inefficient, with a success rate of less than 3% in rodents and even lower in farm animal species. These low efficiency rates correlate directly with high production costs, thus hampering the production of transgenic swine.

Viral transgenesis using retroviral vectors has met with limited success, but researchers have recently used lentiviruses—members of a family of complex retroviruses—to create transgenic mice. Lentiviruses infect both dividing and nondividing cells, infect a broad variety of cells, and transduce murine and human embryonic stem cells and preimplantation embryos.

Now, a group led by Eckhard Wolf and Alexander Pfeifer of the Ludwig-Maximilians University in Munich, Germany, report using a lentiviral vector carrying the green fluorescent protein (GFP) transgene and a ubiquitous promoter to produce transgenic swine (EMBO Rep., November 2003). They injected the vector into single-cell embryos and implanted these into recipient females. Of the 46 piglets born, 32 (70%) carried the transgene, and 30 (94%) of these showed GFP expression in all tissues. The group also demonstrated that the transgene was transmitted through the germline and that a tissue-specific promoter could be used to limit the expression of the transgene to specific tissues.

According to Pfeifer, the group will now attempt to generate strains of pigs carrying transgenes relevant to xenotransplantation. He tells Lab Animal, “The combination of lentiviral transgenesis and RNAi technology should allow for the expression of foreign genes as well as the knockdown of porcine genes from one and the same vector.”