Abstract: The invention provides a lentiviral vector capable of inhibiting the expression of at least one target gene. A lentiviral vector of the invention encompasses a first nucleic acid sequence derived from a target gene transcript and a second nucleic acid sequence corresponding to the reverse complement of said first nucleic acid sequence. A lentiviral vector of the invention capable of inhibiting the expression of a target gene is useful in therapeutic applications to inactivate disease-associated transcripts and thereby reduce the severity of inherited metabolic, infectious or malignant conditions. Methods for inhibiting one or more target genes in a cell as well as methods for producing a non-human mammal in which the expression of one or more target genes is inhibited also are provided by the present invention.