The Children's Hospital of Philadelphia

Sangamo Biosciences, Inc.

University of Pennsylvania

The University of North Carolina at Chapel Hill

Academisch Ziekenhuis Bij De Universiteit Van Amsterdam

Elkouby, Liron

Sabatino, Denise

High, Katherine A.

Katherine A High

Federico Mingozzi

Xavier Anguela

John Fraser Wright

Bernd Hauck

Guang Qu

Mustafa N Yazicioglu

Philip D Gregory

Roland W Herzog

Michael C Holmes

Marcela V Maus

Rodney M Camire

Daniel J Hui

Hojun Li

Jean Bennett

Darrel W Stafford

Junwei Sun

Valder R Arruda

Albert M Maguire

J Fraser Wright

Olga Zelenaia

Paul A Fields

Peter J Larson

Yifeng Chen

Philip Johnson

Samuel Murphy

Luca Monaldini

Fayaz R Khazi

Gregory Podsakoff

Sarah McCague

Jennifer Wellman

Daniel Chung

Liron Elkouby

Denise Sabatino

Kirk Chu

Christoffel Arnoldus Spek

Geerte Van Sluis

Mustafa Yazicioglu

Albert Maguire

Sarah Mccague

The invention relates to adeno-associated virus (AAV) serotype AAV-Rh74 and related AAV vectors, and AAV-Rh74 and related AAV vector mediated gene transfer methods and uses. In particular, AAV-Rh74 targets polynucleotides to cells, tissues or organs for expression (transcription) of genes encoding therapeutic proteins and peptides, and polynucleotides that function as or are transcribed into inhibitory nucleic acid sequences.

AAV vector compositions and methods for gene transfer to cells, organs and tissues

The invention relates to modified Factor IX coding sequence, expression cassette, vectors such as viral (e.g., lenti- or adeno-associated viral) vectors, and gene transfer methods and uses. In particular, to target Factor IX nucleic acid to cells, tissues or organs for expression (transcription) of Factor IX.

Modified factor IX, and compositions, methods and uses for gene transfer to cells, organs, and tissues

Methods for preparing highly purified AAV vector formulations are provided. The highly pure AAV formulations described herein are superior for clinical use.

Scalable manufacturing platform for viral vector purification and viral vectors so purified for use in gene therapy

In accordance with the present invention, a method for increasing the yield of rLV vector particles comprising a trans gene encoding a therapeutic protein or fragment thereof is disclosed. In one approach, cells are transfected with plasmids encoding the necessary components for rLV production using a calcium chloride transfection mix at pH 7.1 wherein the calcium chloride and plasmids form a complex which is added to the cells at a constant speed. The cells are then incubated for a suitable time period wherein virus particle media is collected at least twice during the incubation period and stored in a cold storage unit, thereby reducing virus inactivation.

Large commercial scale lentiviral vector production system and vectors produced thereby

Compositions and methods are provided for inhibiting T cell mediated destruction of virally transduced, trangene containing cells.

Compositions and methods for detection and modulation of T cell mediated immune responses against viral vectors utilized for gene therapy

Virus vectors, virus particles, and methods and uses of screening for, detecting, analyzing and determining amounts of virus antibody, or neutralizing antibody activity of samples are provided. Such virus vectors, virus particles, and methods and uses are applicable to a broad range of virus types, such as lentiviruses, adenovirus, and adeno-associated virus (AAV) serotypes. Methods and uses include virus antibody screening, such as anti-virus immunoglobulins screened for, detected, analyzed and amounts determined.

AAV vector and assay for anti-AAV (adeno-associated virus) neutralizing antibodies

Compositions and methods for AAV mediated gene therapy are disclosed. AAV vectors comprise protein capsid variants comprising therapeutically beneficial transgenes. AAV variants are provided which exhibit increased transduction efficiency when compared to AAV serotypes (e.g., AAV1, AAV2, AAV8, AAV-rh74), which lack the modifications disclosed herein. Such improved vectors are useful for transduction of a variety of tissues.

Composition and methods for highly efficient gene transfer using AAV capsid variants

Factor VIII variants and methods of use thereof are disclosed. In particular embodiments, Factor VIII variants are expressed more efficiently by cells over wild-type Factor VIII proteins, are secreted at increased levels by cells over wild-type Factor VIII proteins, exhibit enhanced activity over wild-type Factor VIII proteins and are packaged more efficiently into viral vectors.

Expression cassette for packaging and expression of variant factor VIII for the treatment of hemostasis disorders

The invention provides viral vector formulations and methods of uses thereof for delivery of transgenes or therapeutic nucleic acids to human subjects. The formulations include a vector and suitable amounts of empty capsids, viral genome-containing capsids, or viral capsid proteins which are optionally chemically or structurally modified and which bind to neutralizing anti-AAV antibodies thereby reducing or preventing antibody-mediated clearance of the vector, but still allowing the genome-containing (therapeutic) vector to transduce target cells and achieve therapeutic gene transfer.

Virus vectors for highly efficient transgene delivery

A test of visual function and/or functional vision may be performed at varying luminance levels. A first course may be selected for a subject. A given course may comprise a layout having a beginning point, at least one turn, at least one obstacle, and an ending point. The first course may be illuminated with a first luminance level based on an estimated lower light sensitivity cutoff. The subject may be prompted to perform a first run of the test. The test may comprise, from the beginning point to the ending point, navigating the layout of the first course by walking around the at least one turn and avoiding the at least one obstacle. A determination may be made as to whether the subject successfully completed the first course based on one or both of speed or accuracy.

Apparatus and methods for testing visual function and functional vision at varying luminance levels

This application relates to the fields of gene therapy and molecular biology. In accordance with the present invention, an adeno-associated virus (AAV) vector comprising an altered capsid protein is provided. More specifically, this invention provides adeno-associated viral vectors comprising protein capsid variants which accelerate vector breakdown and clearance, thereby reducing undesirable immune responses.

AAV8 vector with enhanced functional activity and methods of use thereof

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Merion Station, PA, United States of America

Katherine A High