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: A battery-powered motorized window treatment for covering at least a portion of a window may be adjusted into a service position to allow for access to at least one battery that is powering the motorized window treatment. A headrail of the motorized window treatment may be adjusted to the service position to allow for easy replacement of the batteries without unmounting the headrail and without requiring tools. The motorized window treatment may comprise brackets having buttons that may be actuated to release the headrail from a locked position, such that the head rail may be rotated into the service position. The headrail easily rotates through a controlled movement into the service position, such that a user only needs one free hand available to move the motorized window treatment into the service position and change the batteries.

Abstract: The invention provides a polynucleotide sequence (e.g., a gene, e.g., DNA or RNA) encoding UGT1A1 (e.g., expressing human UGT1A1). The invention further provides a vector, such as an adeno-associated virus (AAV) vector (e.g., AAV8) having a vector genome including inverted terminal repeat sequences and a UGT1A1 coding sequence operably linked to one or more expression control sequences (e.g., expression control sequences including a liver-specific promoter). Also provided are compositions containing these AAV vectors and methods of treating Crigler-Nijjar syndrome type I, Crigler-Nijjar syndrome type II, and Gilbert syndrome.

Abstract: Provided herein are compositions including brain-capillary binding and/or blood-brain barrier crossing (BBB) tissue-targeting peptides linked thereto or inserted in a targeting protein of a recombinant vector having at least one exogenous peptide comprising an amino acid sequence of Y-G/A/R/K-Y/H-GNPA-T/R/H-RYFD-V/K. Compositions providing such conjugates, targeting peptides, or recombinant vectors having a mutant capsid or envelope protein are provided as are uses thereof.

Abstract: A dual vector system for treating a genetic disorder is provided. The system includes (a) a gene editing vector comprising an expression cassette comprising a nucleic acid sequence encoding a nuclease and regulatory sequences that direct expression of the nuclease in a target cell comprising a PCSK9 gene; and (b) a donor vector comprising a nucleic acid sequence encoding an exogenous product for expression from the PCSK9 locus, wherein the inserted nucleic acid sequence does not encode PCSK9, wherein the system further comprises sequences that direct the nuclease to specifically targets the native PCSK9 gene locus; and wherein the native PCSK9 in the target cell is optionally ablated or reduced post-dosing with the dual vector system.

Abstract: Compositions useful for treatment of Spinal and Bulbar Muscular Atrophy (SBMA) comprising administration of a recombinant adeno-associated virus (rAAV) vector having an AAV capsid and a vector genome comprising a sequence encoding at least one hairpin forming miRNA that comprises a targeting sequence which binds a target site on the mRNA of human androgen receptor, wherein the miRNA inhibits expression of human androgen receptor, is provided. Also provided are compositions containing a rAAV vector and methods of treating SBMA in patient comprising administration of a rAAV vector.

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 recombinant adeno-associated virus (rAAV) vector comprising an AAVhu68 capsid produced in a production system comprising a nucleotide sequence of SEQ ID NO: 1, or a sequence at least 75% identical thereto which encodes SEQ ID NO:2. The AAVhu68 capsid comprises subpopulations of highly deamidated asparagine residues in asparagine-glycine pairs in the amino acid sequence of SEQ ID NO: 2. Also provided are compositions containing the rAAV and uses thereof. Additionally, rAAV having an engineered AAV capsid comprising at least one subpopulation of vp1 or vp2 proteins having a Val at amino acid position 157 with reference to the AAVhu68 vp1 numbering are provided.

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: Provided herein are polynucleotide sequences encoding human acid sphingomyelinase (SMPD1) and expression cassettes containing these coding sequences. Also provided are vectors, such as recombinant adeno-associated virus (rAAV) vectors having vector genomes that include an engineered SMPD1 coding sequence operably linked to one or more regulatory sequences. Further, compositions containing these expression cassettes and rAAV are provided, as well as methods for the use of these compositions for treatment of Niemann Pick Type A disease.

Abstract: An apparatus including a body, a shaft assembly extending distally from the body, and an end effector configured to grasp and transmit RF energy to the tissue. The end effector includes a first jaw having a first tissue grasping feature and a second jaw. The second jaw is pivotably coupled to the first jaw between an open position, a partially closed position, and a closed position. The second jaw includes a proximal taper having a proximal electrode surface, a distal taper including a distal electrode surface, and a juncture between the proximal and distal electrode surface. The juncture is spaced further from the first tissue grasping feature compared to the proximal and distal end while the second jaw is in the partially closed position. The proximal and distal electrode surface deform to define a gap with the first tissue grasping feature while in the closed position.

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 recombinant adeno-associated virus (rAAV) comprising an AAV capsid and a vector genome comprising a frataxin gene is provided. Also provided is a composition containing an effective amount of rAAV to ameliorate symptoms of Freidreich's ataxia, including, e.g., reduction in progression towards neurocognitive decline and/or cardiomyopathy.

Abstract: A co-therapeutic regimen comprising AAV9-mediated intrathecal/intracisternal and/or systemic delivery of an expression cassette containing a hIDUA gene and two or more immunosuppressants is provided herein. Also provided are methods useful for treating hIDUA deficiency (MPSI) and the symptoms associated with Hurler, Hurler-Scheie and Scheie syndromes.

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: Provided herein are compositions including targeting peptides linked thereto or inserted in a targeting protein of a recombinant vector having at least one exogenous peptide comprising an amino acid sequence of N-x-(T/I/V/A)-(K/R) (SEQ ID NO: 47). Compositions providing such conjugates, targeting peptides, or recombinant vectors having a mutant capsid or envelope protein are provided as are uses thereof.

Abstract: A co-therapeutic regimen comprising AAV9-mediated intrathecal/intracisternal and/or systemic delivery of an expression cassette containing a hIDS gene and two or more immunosuppressants is provided herein. Also provided are methods and kits containing these vectors and compositions useful for treating Hunter syndrome and the symptoms associated with Hunter syndrome.

Abstract: Compositions and methods for treating diabetes in a canine are provided. A viral vector is provided which includes a nucleic acid molecule comprising a sequence encoding a canine insulin polypeptide.

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 functional human N-acetyl-alpha-glucosaminidase (hNAGLU), a regulatory sequence which direct expression of hNAGLU in a target cell, and an AAV 3? ITR. Also provided is a pharmaceutical composition comprising a rAAV as described herein in a formulation buffer, and a method of treating a human subject diagnosed with MPS IIIB.

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.