ABSTRACT

The present invention provides methods and compositions for the integration of a nucleotide sequence of interest into the genome. Specifically, the methods of the present invention comprise contacting a lentiviral vector with the plasma membrane of an oocyte, early stage embryo, or blastula under conditions that permit the entry of the viral vector and the subsequent integration of the nucleotide sequence of interest into the genome. The methods further comprise culturing the oocyte or embryo contacted with the lentiviral vector under conditions that allow for the formation of a pre-implantation embryo. Subsequently, the pre-implantation embryo can be transferred into a recipient vertebrate where it is allowed to develop into at least one genetically modified animal. The methods and compositions of the invention thereby allow for the production of genetically modified animals, particularly, vertebrates, and particularly mammals.