Abstract: A recombinant adeno-associated virus (AAV) having an AAV capsid and packaged therein a heterologous nucleic acid which expresses two functional antibody constructs in a cell is described. Also described are antibodies comprising a heavy chain and a light chain from a heterologous antibody. In one embodiment, the antibodies are co-expressed from a vector containing: a first expression cassette which encodes at least a first open reading frame (ORF) for a first immunoglobulin under the control of regulatory control sequences which direct expression thereof; and a second expression cassette which comprises a second ORF, a linker, and a third ORF under the control of regulatory control sequences which direct expression thereof, wherein the second and third ORF for a second and third immunoglobulin construct. The vector co-expressing these two antibody constructs is in one embodiment an AAV, in which the 5? and 3? ITRs flank the expression cassettes and regulatory sequences.

Abstract: A suspension useful for AAV9-mediated intrathecal/intracisternal and/or systemic delivery of an expression cassette containing a hIDUA gene is provided herein. Also provided are methods and kits containing these vectors and compositions useful for treating MPSI and the symptoms associated with Hurler, Hurler-Scheie and Scheie syndromes.

Abstract: A liquid suspension product comprising a recombinant adeno-associated virus (rAAV) having an AAV8 capsid which is suitable for intra-retinal injection is provided herein. Also provided herein are liquid suspensions containing these rAAV8.aVEGF and methods of using same for treatment of wet AMD and other ocular conditions.

Abstract: Provided herein is a recombinant AAV (rAAV) comprising an AAV capsid and a vector genome packaged therein, wherein the vector genome comprises an AAV 5? inverted terminal repeat (ITR), an engineered nucleic acid sequence encoding a gene product for expression in target cells, and miRNA target sequences which selectively repress expression in dorsal root ganglion (DRG) cells. Also provided is a pharmaceutical composition comprising a rAAV as described herein in a formulation buffer, and a method of treating a human subject with CNS-targeted gene therapy while selectively preventing expression in DRG cells.

Abstract: A method of correcting singletons in a selected AAV sequence in order to increasing the packaging yield, transduction efficiency, and/or gene transfer efficiency of the selected AAV is provided. This method involves altering one or more singletons in the parental AAV capsid to conform the singleton to the amino acid in the corresponding position(s) of the aligned functional AAV capsid sequences.

Abstract: An artificial AAV capsid comprising a heterologous conducting airway targeting sequence is provided. The artificial AAV is useful as a targeting moiety, for delivery of heterologous molecules which are associated therewith. The artificial AAV is also useful in the generation of AAV vectors having the artificial capsid. Also described are methods of modifying the native tropism and transduction efficiency of vectors by improving and/or ablating their ability to transduce conducting airway cells. Methods of targeting conducting airway cells and delivering therapeutic and other molecules thereto are also provided.

Abstract: A method of altering the targeting and/or cellular uptake efficiency of an adeno-associated virus (AAV) viral vector having a capsid containing an AAV9 cell surface binding domain is described. The method involves modifying a clade F cell surface receptor which comprises a glycan having a terminal sialic acid residue and a penultimate ?-galactose residue. The modification may involve retargeting the vector by temporarily functionally ablate AAV9 binding in a subset of cells, thereby redirecting the vector to another subset of cells. Alternatively, the modification may involve increasing cellular update efficiency by treating the cells with a neuraminidase to expose cell surface ?-galactose. Also provided are compositions containing the AAV9 vector and a neuraminidase. Also provided is a method for purifying AAV9 using ?-galactose linked to solid support.

Abstract: A method of correcting singletons in a selected AAV sequence in order to increasing the packaging yield, transduction efficiency, and/or gene transfer efficiency of the selected AAV is provided. This method involves altering one or more singletons in the parental AAV capsid to conform the singleton to the amino acid in the corresponding position(s) of the aligned functional AAV capsid sequences.

Abstract: Compositions and regimens useful in treating hemophilia A are provided. The compositions include recombinant adeno-associated virus (rAAV) with a transthyretin enhancer and promoter driving expression of a human Factor VIII.

Abstract: Compositions and regimens useful in reducing one or more of: LDL-cholesterol, total cholesterol, and/or fasting triglycerides in a subject, and/or modifying fractional catabolic rate (FCR) of LDL apolipoprotein B (apoB) from baseline to a selected time point after rAAV administration are provided. The method involves administering to the human subject via a peripheral vein by infusion of a suspension of replication deficient recombinant adeno-associated virus (rAAV).

Abstract: A recombinant adeno-associated virus (rAAV) vector comprising an AAV capsid having a heterogeneous population of vp1 proteins, a heterogeneous population of vp2 protein and a heterogeneous population of vp3 proteins. The capsid contains modified amino acids as compared to the encoded VP1 amino acid sequence, the capsid containing highly deamidated asparagine residues at asparagine-glycine pair, and further comprising multiple other, less deamidated asparagine and optionally glutamine residues. Methods of reducing deamidation in the AAV capsid of a rAAV are provided.

Abstract: A vector have an expression cassette containing have a hIDUA gene has a sequence of SEQ ID NO: 1 (FIG. 1) or a sequence at least about 95% identical thereto which encodes a functional human alpha-L-iduronidase is provided. The vector may be a production vector or a rAAV8. Also provided are compositions containing these vectors and methods of treating MPSI and the symptoms associated with Hurler, Hurler-Scheie and Scheie syndromes.

Abstract: A non-replicating recombinant adeno-associated associated virus (rAAV) having an AAV capsid having packaged therein a vector genome which comprises AAV inverted terminal repeat sequences and at least one nucleic acid sequence encoding four different immunoglobulin regions (a), (b), (c) and (d) is provided. The rAAV-expressed immunoglobulins are useful for providing passive immunization against influenza A and influenza B. Also described herein are compositions containing the rAAV. Methods of vaccinating patients against influenza are provided.

Abstract: A method for producing AAV, without requiring cell lysis, is described. The method involves harvesting AAV from the supernatant. For AAV having capsids with a heparin binding site, the method involves modifying the AAV capsids and/or the culture conditions to ablate the binding between the AAV heparin binding site and the cells, thereby allowing the AAV to pass into the supernatant, i.e., media. Thus, the method of the invention provides supernatant containing high yields of AAV which have a higher degree of purity from cell membranes and intracellular materials, as compared to AAV produced using methods using a cell lysis step.

Abstract: Viral vectors comprising engineered hOTC DNA and RNA sequences are provided which when delivered to a subject in need thereof are useful for treating hyperammonemia, ornithine transcarbamylase deficiency and symptoms associated therewith. Also provided are methods of using hOTC for treatment of liver fibrosis and/or cirrhosis in OTCD patients by administering hOTC.

Abstract: A composition comprising at least one AAV vector formulated for central nervous system delivery is described. The composition comprises at least one expression cassette which contains sequences encoding an anti-neoplastic immunoglobulin construct for delivery to the brain operably linked to expression control sequences therefor and a pharmaceutically acceptable carrier. The anti-neoplastic immunoglobulin construct may be an immunoglobulin modified to have decreased or no measurable affinity for neonatal Fc receptor (FcRn). Also provided are methods of using these constructs in preparing pharmaceutical compositions and uses thereof in anti-neoplastic regimens, particularly for primary and/or metastatic cancers of the brain.

Abstract: A pathogen detection and display system is configured to discover and display the location of substances of interest, particularly pathogens that can spread infection. The detection and display system can be used in healthcare facilities on surfaces, medical equipment and devices, patients, and staff, for example.

Abstract: A method of correcting singletons in a selected AAV sequence in order to increasing the packaging yield, transduction efficiency, and/or gene transfer efficiency of the selected AAV is provided. This method involves altering one or more singletons in the parental AAV capsid to conform the singleton to the amino acid in the corresponding position(s) of the aligned functional AAV capsid sequences.

Abstract: A vector have an expression cassette containing have a hIDUA gene has a sequence of SEQ ID NO: 1 (FIG. 1) or a sequence at least about 95% identical thereto which encodes a functional human alpha-L-iduronidase is provided. The vector may be a production vector or a rAAV8. Also provided are compositions containing these vectors and methods of treating MPSI and the symptoms associated with Hurler, Hurler-Scheie and Scheie syndromes.

Abstract: A non-replicating recombinant adeno-associated associated virus (rAAV) having an AAV capsid having packaged therein a vector genome which comprises AAV inverted terminal repeat sequences and at least one nucleic acid sequence encoding four different immunoglobulin regions (a), (b), (c) and (d) is provided. The rAAV-expressed immunoglobulins are useful for providing passive immunization against influenza A and influenza B. Also described herein are compositions containing the rAAV. Methods of vaccinating patients against influenza are provided.