University of Pennsylvania

Analog Devices,inc.

Other

Whitehead Institute for Biomedical Research

University of Michigan

The Wistar Institute of Anatomy & Biology

Howard Hughes Medical Institute

Mra Laboratories, Inc.

The Brigham and Women's Hospital, Inc.

Janssen Biotech, Inc.

New England Medical Center Hospitals. Inc.

Somatix Therapy Corporation

Howard Hughes Medical Center

James M Wilson

Guangping Gao

Mauricio R Alvira

Luc H Vandenberghe

Soumitra Roy

Ronald A Cellini

Christian Hinderer

Anna P Tretiakova

Krishna J Fisher

James M Sobol

Lili Wang

Yosef Stein

Luk H Vandenberghe

Colm J Prendergast

Joshua A Kablotsky

Weidong Xiao

Jenny Agnes Sidrane

Richard C Mulligan

Christopher Mayer

Gregory M Yukna

Qiang Wang

Juliette Hordeaux

Guang-Ping Gao

Christie L Bell

Karen Kozarsky

Daniel Boyko

Jerome Frank Strauss, Iii

Nathan Katz

William M Kelley

Giorgio Trinchieri

Daniel J Rader

Martin Lock

John F Engelhardt

Yiping Yang

William Thomas Rothwell

Alberto Auricchio

Lawrence K Cohen

Olafur Mar Josefsson

Brittney Gurda

Markus Hildinger

April Tepe

Maria P Limberis

Hildegund C Ertl

Shu-Jen Chen

Matthew Weitzman

Louis K Birinyi

Daniel Phaneuf

Matthew Wilson

Mark L Anderson

Michael A Zasloff

Francis S Collins

Michael Naso

Galeb H Maher

Joost Alexander Kolkman

Paul F Ferguson, Jr

Hildegund C J Ertl

Lewis F Lahr

Stuart Patterson

Lakshmanan Govindasamy

Richard P Schubert

Benoit Dufort

Maria A Croyle

Kevin T Turner

James H Wilson

Liang Chai

Samir G Maher

Youhai H Chen

Alan Rae

Lori F Rafield

Harry E Trout

Joseph E Rabinowitz

Kevin Turner

Nimrod Miller

Joshua Joyner Sims

Robert Friesen

Dean M Wilson

Allan D Callow

Scott Ashley

Steven F Farina

Ethan D Stolzenberg

Prasad Kari

Mitchell Goldman

Robert Bals

Suryanrayan Somanathan

Lew Lahr

Susan M Faust

Jenny Agnes Greig

Matthew Aaron Hazel

Yan Zhi

John F Wilson

Brittney L Gurda

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 inverted terminal repeat (ITR) sequence; (b) a promoter; (c) a CLN2 coding sequence encoding a human TPP1; (d) an AAV 3' ITR.

Gene therapy for ceroid lipofuscinoses

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.

Adeno-associated virus (AAV) vectors, AAV vectors having reduced capsid deamidation and uses therefor

A recombinant AAV (rAAV) suitable for use in treating adult onset neurodegeneration caused by granulin (GRN) haploinsufficiency, such as progranulin (PGRN)-related frontotemporal dementia (FTD), is provided. The rAAV comprises (a) an adeno-associated virus 1 capsid, and (b) a vector genome packaged in the AAV capsid, said vector genome comprising AAV inverted terminal repeats, a coding sequence for human progranulin, and regulatory sequences which direct expression of the progranulin. Also provided are a method for treating a human patient with PGRN-FTD and other adult onset neurodegeneration caused by granulin (GRN) haploinsufficiencies, comprising delivering to the central nervous system (CNS) a recombinant adeno-associated virus (rAAV) having an adeno-associated virus 1 (AAV1) capsid, said rAAV further comprising a vector genome packaged in the AAV capsid, said vector genome comprising AAV inverted terminal repeats, a coding sequence for human progranulin, and regulatory sequences which direct expression of the progranulin.

Recombinant adeno-associated virus for treatment of GRN-associated adult-onset neurodegeneration

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).

Gene therapy for treating citrullenemia

Provided is a recombinant adeno-associated virus (rAAV) having an AAVhu68 capsid and a vector genome which comprises a nucleic acid sequence encoding a functional human arylsulfatase A (ARSA). 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 metachromatic leukodystrophy, or ameliorating symptoms of metachromatic leukodystrophy, or delaying progression of metachromatic leukodystrophy via administering an effective amount of rAAV to a subject in need thereof.

Compositions useful in treatment of metachromatic leukodystrophy

Compositions and methods for treating type II diabetes in a subject. A viral vector is provided which includes a nucleic acid molecule comprising a sequence encoding a propeptide and the active portion of GLP-1, wherein, when expressed, the N-terminal amino acid of GLP-1 immediately follows the C-terminal amino acid of the propeptide. In desired embodiments, the subject is a cat or dog.

GLP-1 and use thereof in compositions for treating metabolic diseases

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.

Composition for treatment of Crigler-Najjar syndrome

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.

AAV9-mediated gene therapy for treating mucopolysaccharidosis type I

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.

Methods and compositions for treating metastatic breast cancer and other cancers in the brain

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.

Adeno-associated virus (AAV) clade f vector and uses therefor

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.

Gene therapy for treating Mucopolysaccharidosis type II

A recombinant vector comprises simian adenovirus 43, 45, 46, 47, 48, 49 or 50 sequences and a heterologous gene under the control of regulatory sequences. A cell line which expresses simian adenovirus 43, 45, 46, 47, 48, 49 or 50 gene(s) is also disclosed. Methods of using the vectors and cell lines are provided.

Simian adenoviruses SAdV-43, -45, -46, -47, -48, -49, and -50, and uses thereof

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.

Gene therapy for treating hemophilia A

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 &#x3b2;-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 &#x3b2;-galactose. Also provided are compositions containing the AAV9 vector and a neuraminidase. Also provided is a method for purifying AAV9 using &#x3b2;-galactose linked to solid support. Also provided are mutant vectors which have been modified to alter their targeting specificity, including mutant AAV9 in which the galactose binding domain is mutated and AAV in which an AAV9 galactose binding domain is engineered.

Compositions and methods for altering tissue specificity and improving AAV9-mediated gene transfer

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.

Compositions useful in treatment of ornithine transcarbamylase (OTC) deficiency

Growing community of inventors

Philadelphia, PA, United States of America

James M Wilson