Abstract: A pseudotyped rAAV is described, which contains sequences derived from AAV5. A method for producing rAAV pseudotyped with AAV5 capsid is described in which the rep proteins of the serotype or any cross-reactive serotype of the AAV ITRs are utilized. A similar method may be provided to generate a pseudotyped rAAV in which minigenes carrying AAV5 ITRs are packaged in capsids of a heterologous AAV serotype. Also provided are pharmaceutical compositions containing the pseudotyped rAAV and methods of using them for gene delivery.

Abstract: Decreasing the expression of genes in a mammalian subject has multiple applications ranging from cancer therapy to anti-infective therapy or treatment of autosomal dominant genetic disorders. Yet, there is still a lack of efficient technologies to achieve that goal in mammalian subjects in vivo. The present invention relates to methods for decreasing gene expression by administering to a mammalian subject a recombinant adeno-associated viral vector in vivo with said vector comprising an RNA interference (RNAi) expression cassette whose RNA expression products directly or indirectly lead to a decrease in expression of the corresponding RNAi target gene. Upon successful transduction with the recombinant adeno-associated viral vector, the RNA expression products of the RNAi expression cassette will decrease the cellular concentration of the mRNA transcripts of the RNAi target gene, thus resulting in decreased concentration of the protein encoded by the RNAi target gene.

Abstract: Cancer is a major cause of death in developed countries. Yet, there is still a high degree of unmet need in the prevention, treatment and/or cure of cancer. The present invention relates to methods for treating cancer, preventing cancer and/or inhibiting the growth of cancer (cells) by administering to a mammalian subject a gene transfer vector in vivo comprising a nucleic acid composition whose expression directly or indirectly leads to the expression and/or secretion of Tissue inhibitor of metalloproteinase-3 (TIMP-3). Upon successful transduction, expression and/or secretion of TIMP-3—either locally (in the vicinity or within the cancer cells) or systemically—will inhibit cancer growth. Also provided are pharmaceutical kits containing the gene transfer vector in a suitable pharmaceutical suspension for administration.

Abstract: A method for isolating, from a mixture, a virus having a surface protein with a binding site for sialic acid is provided. The method involves contacting the mixture with mucin which has been linked to a solid support and washing the solid support to remove material from the mixture which is non-specifically bound to the mucin-linked support. Thereafter, the specifically bound virus (e.g., AAV4 or AAV5) may be removed in a further washing step utilizing a concentrated salt or solution with low pH. Also described are pharmaceutical kits containing solid supports linked to mucin for use in isolating virus having a surface protein with a binding site for sialic acid, or detecting the presence of the virus in a biological sample.

Abstract: A pseudotyped rAAV is described, which contains sequences derived from AAV5. A method for producing rAAV pseudotyped with AAV5 capsid is described in which the rep proteins of the serotype or any cross-reactive serotype of the AAV ITRS are utilized. A similar method may be provided to generate a pseudotyped rAAV in which minigenes carrying AAV5 ITRs are packaged in capsids of a heterologous AAV serotype. Also provided are pharmaceutical compositions containing the pseudotyped rAAV and methods of using them for gene delivery.

Abstract: A non-invasive method for obtaining therapeutic levels of protein in the bloodstream by administering rAAV containing a transgene encoding the secretable or extracellular membrane-bound protein via inhalation, is provided. Suitably, the transgene product is under the control of a lung-specific promoter. Also provided are pharmaceutical kits containing rAAV encoding the secretable protein in a suspension suitable for delivery via intranasal or oral inhalation.