Abstract: Provided is a recombinant adeno-associated virus (rAAV) having an AAV capsid and a vector genome which comprises a nucleic acid sequence encoding a functional CDKL5 (hCDKLK5). Also provided are a production system useful for producing the rAAV, a pharmaceutical composition comprising the rAAV, and a method of treating a subject having CDD, or ameliorating symptoms of CDD, or delaying progression of CDD via administrating an effective amount of the rAAV to a subject in need thereof.

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: Provided herein are methods and compositions for treatment of Batten disease. Such compositions include a recombinant adeno-associated virus (rAAV), said rAAV comprising an AAV capsid, and a vector genome packaged therein, said vector genome comprising (a) an AAV 5? inverted terminal repeat (ITR) sequence; (b) a promoter; (c) a CLN2 coding sequence encoding a human TPP1; (d) an AAV 3? ITR.

Abstract: A rAAV vector is described herein which has an AAVhu68 capsid and at least one expression cassette in the capsid. The at least one expression cassette comprises nucleic acid sequences encoding a functional SMN protein and expression control sequences that direct expression of the SMN sequences in a host cell. Also provided are compositions containing this rAAVhu68.SMN vector and methods of using same for spinal muscular atrophy in a patient.

Abstract: A recombinant adeno-associated virus (rAAV) comprising an AAVhu68 capsid and a vector genome comprising a lysosomal beta-galactosidase gene (for example, galactosidase beta 1 gene, GBL1) is provided (i.e., rAAVhu68.GBL1). Also provided a composition containing an effective amount of rAAVhu68.GBL1 to ameliorate symptoms of GM1 gangliosidosis, including, e.g., increased average life span, decreased need for feeding tube, reduction in seizure incidence and frequency, reduction in progression towards neurocognitive decline and/or improvement in neurocognitive development.

Abstract: A recombinant vector having an expression cassette is provided which comprises a modified human low density lipoprotein receptor (hLDLR) gene is provided, wherein said hLDLR gene encodes a modified hLDLR comprising (a) one or more of the following amino acid substitutions: L318H, N295D, H306D, V307D, N309A, D310N, L318H, and/or L318D; or (b) an amino acid substitution of any of (a) in combination with one or more of the following amino acid substitutions: K796, K809R and/or C818A. Also provided are pharmaceutical compositions containing this vector and uses therefor in lowering cholesterol and/or treating familial hypercholesterolemia.

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 hSGSH, a regulatory sequence which direct expression of hSGSH 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 IIIA.

Abstract: Regimens useful in reducing the frequency of apheresis in a human patient having familial hypercholesterolemia are described. 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: Provided herein are novel AAV capsids and rAAV comprising the same. In one embodiment, vectors employing the AAV capsid show increased transduction in a selected tissue as compared to a prior art AAV.

Abstract: Various aspects of a generator, ultrasonic device, and method for estimating and controlling a state of an end effector of an ultrasonic device are disclosed. The ultrasonic device includes an electromechanical ultrasonic system defined by a predetermined resonant frequency, including an ultrasonic transducer coupled to an ultrasonic blade. A control circuit measures a complex impedance of an ultrasonic transducer, wherein the complex impedance as defined as Z g ( t ) = V g ( t ) I g ( t ) ; The control circuit receives a complex impedance measurement data point and compares the complex impedance measurement data point to a data point in a reference complex impedance characteristic pattern. The control circuit then classifies the complex impedance measurement data point based on a result of the comparison analysis and assigns a state or condition of the end effector based on the result of the comparison analysis.

Abstract: Compositions and regimens useful in treating type I citrullenemia are provided. The compositions include recombinant adeno-associated virus (rAAV) with a transthyretin enhancer and promoter driving expression of a human Argininosuccinate Synthase 1 (ASS1).

Abstract: AAV vectors expressing anti-influenza antibodies are provided. Also described are pharmaceutical compositions useful in delivery same for prophylactic or anti-viral purposes. Methods of delivering such vectors are provided.

Abstract: Provided herein are nucleic acid sequence encoding hIDUA and expression cassettes containing these coding sequences. Also provided are vectors, such as recombinant adeno-associated virus (rAAV) vectors having a vector genome including a hIDUA coding sequence operably linked regulatory sequences that direct expression of the hIDUA. Also provided are compositions containing these expression cassettes and rAAV vectors and methods of treating MPS1 or an associated syndrome such as Hurler, Hurler-Scheie and/or Scheie syndrome. The compositions and methods provided are further designed to selectively repress expression of hIDUA in dorsal root ganglia.

Abstract: Compositions and regimens useful in treating Wilson's Disease are provided. The compositions include recombinant adeno-associated virus (rAAV) with a transthyretin enhancer and promoter driving expression of a human ATP7B.

Abstract: Provided herein are combination therapies involving co-expression of an E2 subunit of a branched-chain alpha-keto acid dehydrogenase (BCKDH) from a skeletal muscle-targeted rAAV.hDBT vector and a liver-targeted rAAV.hDBT vector. Also provided herein are combination therapies wherein an E1a and/or an E1b subunit of the BCKDH complex is expressed from muscle and/or liver following rAAV-mediated delivery targeted to these tissues. Further 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 MSUD.

Abstract: Surgical instruments and system and methods for using surgical instruments are disclosed. A surgical instrument comprises an end effector comprising an ultrasonic blade and clamp arm, an ultrasonic transducer, and a control circuit. The ultrasonic transducer ultrasonically oscillates the ultrasonic blade in response to a drive signal from a generator. The end effector receives electrosurgical energy to weld tissue. The control circuit determines a resonant frequency measure indicative of a thermally induced change in resonant frequency and a electrical continuity measure; calculates a weld focal point based on the determined measures, controls closure of the clamp arm to vary a pressure applied by the clamp arm to provide a threshold control pressure to the tissue loaded into the end effector, and maintains a gap between the ultrasonic blade and clamp arm at a point proximal to the proximal end of the tissue. Pressure is varied based on corresponding weld focal point.

Abstract: Adeno-associated virus rh.10 sequences, vectors containing same, and methods of use are provided.

Abstract: Compositions and regimens useful in treating Wilson's Disease are provided. The compositions include recombinant adeno-associated virus (rAAV) with a transthyretin enhancer and promoter driving expression of a human ATP7B.

Abstract: Various aspects of a generator, ultrasonic device, and method for estimating and controlling a state of an end effector of an ultrasonic device are disclosed. The ultrasonic device includes an electromechanical ultrasonic system defined by a predetermined resonant frequency, including an ultrasonic transducer coupled to an ultrasonic blade. A control circuit measures a complex impedance of an ultrasonic transducer, wherein the complex impedance is defined as Z g ? ( t ) = V g ? ( t ) I g ? ( t ) . The control circuit receives a complex impedance measurement data point and compares the complex impedance measurement data point to a data point in a reference complex impedance characteristic pattern. The control circuit then classifies the complex impedance measurement data point based on a result of the comparison analysis and assigns a state or condition of the end effector based on the result of the comparison analysis.

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