Abstract: The present invention relates to AAV vectors comprising a capsid protein that has been modified to bind to high-density lipoprotein (HDL) by insertion of an HDL-binding moiety into the capsid protein. The HDL-binding moiety can be an HDL-binding protein or domain thereof, such as a single domain antibody like a VHH domain, or the HDL-binding moiety can be an HDL-binding epitope, e.g. derived from an HDL- or ApoA1-binding protein. The HDL-binding moiety is preferably inserted into an exposed loop of the capsid protein. The HDL-binding moiety can be expressed on one, two or all three of the VP1, VP2 and VP3 capsid proteins. The AAV vectors of the invention that to bind to HDL show improved transduction efficiency of liver cells as well as improved spread transduction throughout the liver. The invention therefore further provides for the use of the AAV vectors of the invention in the treatment of conditions that can be treated by gene therapy of the liver.

Abstract: The present invention relates to insect cells for producing parvoviral vectors with mosaic, chimeric and/or modified capsids. The insect cells of the invention comprise separate expression cassettes for the VP1 capsid protein and for the VP2 and VP3 proteins, which allow for the production of parvoviral vectors in which the VP1 capsid protein is of a different parvovirus or of a different serotype than the VP2 and VP3 protein and/or for the production of parvoviral vectors in which the VP1 capsid protein is modified, e.g. by the insertion of an exogenous amino acid sequence. Such exogenous amino acid sequence can e.g. encode a single domain antibody that targets the parvoviral vector to a specific tissue or type of cell. The invention further relates to method wherein the insect cells of the invention are used for the production of parvoviral vectors with mosaic, chimeric and/or modified capsids.

Abstract: The present invention relates to a method for producing a single cell clone of an insect cell comprising integrated into the genome of the cell at least one expression cassette for inducible expression of parvoviral Rep 78 and 52 proteins. The insect cells can be used for the production of parvoviral vectors by transfection constructs comprising parvoviral Cap and ITR sequences. Single cell clones obtained in the methods of the invention can be expanded for into a cell bank for the production of clinical grade parvoviral gene therapy vectors.

Abstract: The present invention relates to insect cell lines for the production of parvoviral gene therapy vectors. In particular the invention relates to stable insect cell lines with expression constructs for viral replicase proteins integrated into their genomes, which cell lines allow for high-yield, robust, and scalable production of heterologous parvoviral-related proteins and vectors.

Abstract: The present invention relates novel combinations of nucleic acid constructs for the production of recombinant parvoviral gene therapy vectors. In particular the invention relates a combination preferably no more than two construct, the first construct expressing both the parvoviral Cap and Rep proteins, and the second construct at least comprising the transgene flanked ITRs and optionally again comprising an expression cassette forthe Cap proteins. The nucleic acid constructs are preferably baculoviral vectors for the production of rAAV in insect cells.