Abstract: A genetically modified mammalian cell and genetically modified mammalian cell line comprise a recombination sequence inserted in a target locus on a chromosome of the mammalian cell genome, wherein the recombination sequence comprises Bxb1attB sequence from Mycobacterium smegmatis. A transgenic mammalian cell and transgenic mammalian cell line comprise a heterologous nucleic acid stably integrated in a target locus on a chromosome of the mammalian genome, wherein the heterologous nucleic comprises a heterologous gene configured for expression by the transgenic mammalian cell.

Abstract: A genetically modified mammalian cell and genetically modified mammalian cell line comprise a recombination sequence inserted in a target locus on a chromosome of the mammalian cell genome, wherein the recombination sequence comprises Bxb1attB sequence from Mycobacterium smegmatis. A transgenic mammalian cell and transgenic mammalian cell line comprise a heterologous nucleic acid stably integrated in a target locus on a chromosome of the mammalian genome, wherein the heterologous nucleic comprises a heterologous gene configured for expression by the transgenic mammalian cell.

Abstract: The present invention relates to innovative protoparvoviruses (PV) expressing RNAi effectors, preferably shRNAs, against the CDK9 gene which display improved anticancer activity. These new viruses are based on the ?H-1PVsilencer platform that consists of a protoparvovirus H-1PV featuring an in-frame deletion within the NS region (?H-IPV) and harbouring a shRNA expression cassette in which the expression of the shRNA is controlled by the HI Polymerase III promoter. In this invention the inventors aimed to use the ?H-1PVsilencer to silence the CDK9 gene whose activity is often dysregulated in cancer cells and known to contribute to tumorigenesis. The present invention also provides cells or organisms comprising said parvovirus.