Genetic modification of male germ cells for transgenic species development and gene therapy

摘要

Disclosed is an in vivo method of incorporating exogenous genetic material into the genome of a vertebrate, which involves administering to a male vertebrate's testis a gene delivery mixture comprising a viral vector, such as a retroviral vector, to deliver a polynucleotide encoding a desired trait or product. Also disclosed is an in vitro method of incorporating exogenous genetic material into the genome of a vertebrate, in which germ cells are obtained from a donor male vertebrate and are genetically modified in vitro, before being transferred to a recipient male vertebrate. After the transfer, the male vertebrate bearing the genetically modified germ cells is bred with a female vertebrate such that a transgenic progeny is produced that carries the polynucleotide in its genome. Also disclosed are non-human transgenic vertebrates produced in accordance with the method, including transgenic progeny. A transgenic cell derived from the transgenic vertebrate is also disclosed, being a germ cell, such as a spermatozoan or ovum, a precursor cell of either of these, or a somatic cell. A method of producing a non-human transgenic vertebrate animal line comprising native germ cells carrying in their genome at least one xenogeneic polynucleotide is disclosed, as is vertebrate semen containing the transgenic male germ cells useful in practicing the method.