Avigen, Inc.

Genzyme Corporation

Peter C Colosi

Gary J Kurtzman

Alejandra Elena Arbetman

Michael A Lochrie

Richard T Surosky

Xiaobing Qian

Hideho Okada

Jun Yoshida

Masaaki Mizuno

Linda B Couto

Linda Couto

Georges Natsoulis

George Natsoulis

Yong Zeng

Methods of making and using recombinant AAV virions with decreased immunoreactivity are described. The recombinant AAV virions include mutated capsid proteins or are derived from non-primate mammalian AAV serotypes and isolates that display decreased immunoreactivity relative to AAV-2.

AAV virions with decreased immunoreactivity and uses therefor

The present invention provides methods and compositions for producing high titer, wild-type-free preparations of recombinant AAV ('rAAV') virions. The compositions of the present invention include novel nucleic acids encoding AAV helper functions and AAV helper function vectors. The present invention also includes host cells transfected by the claimed nucleic acids, methods of using the claimed vectors, and rAAV virions produced by such methods.

High-efficiency wild-type-free AAV helper functions

Accessory functions capable of supporting efficient recombinant AAV (rAAV) virion production in a suitable host cell are provided. The accessory functions are in the form of one or more vectors that are capable of being transferred between cells. Methods of producing rAAV virions are also provided. The methods can be practiced to produce commercially significant levels of rAAV particles without also generating significant levels of infectious helper virus or other contaminating by-products.

Accessory functions for use in recombinant AAV virion production

One form of a composition has two types of recombinant adeno-associated virus. The first type encodes a portion of Factor VIII operably linked to an expression control element; and the second type encodes a different portion of Factor VIII operably linked to an expression control element. The first and second nucleotide sequences collectively encode a functional Factor VIII protein. Another form of the composition is a recombinant adeno-associated virus containing a nucleotide sequence encoding functional Factor VIII light or heavy chain operably linked to a tissue-specific promoter.

Adeno-associated vector compositions for expression of Factor VIII

Polynucleotides for use in recombinant adeno-associated virus virion production

The use of recombinant adeno-associated virus (AAV) virions for the treatment of solid tumors is disclosed. The invention provides for the use of recombinant AAV virions to deliver an AAV vector containing a drug-susceptibility gene and a second gene capable of providing an ancillary effect to solid tumor cells. The second gene can be used to enhance the immunogenicity of the transduced tumor cell. Alternatively, the second gene can be used to provide a tumorstatic effect. The invention also provides for the use of recombinant AAV virions to deliver an interferon gene, or a tumor suppressor gene to provide a therapeutic effect in a transduced tumor cell.

Gene therapy for the treatment of solid tumors using recombinant adeno-associated virus vectors

The present invention provides methods and compositions for producing high titer, wild-type-free preparations of recombinant AAV (&ldquo;rAAV&rdquo;) virions. The compositions of the present invention include novel nucleic acids encoding AAV helper functions and AAV helper function vectors. The present invention also includes host cells transfected by the claimed nucleic acids, methods of using the claimed vectors, and rAAV virions produced by such methods.

The present invention provides methods and compositions for producing high titer preparations of recombinant AAV (&ldquo;rAAV&rdquo;) virions. The compositions of the present invention include AAV helper function systems and host cells. The present invention also includes methods of using AAV helper function vectors that effect the production of only small amounts of the long forms of Rep protein, and rAAV virions produced by such methods.

High-efficiency AAV helper functions

The present invention provides improved viral vectors useful for the expression of genes at high levels in human cells. In particular, the present invention provides adeno-associated vectors (AAV) suitable for gene therapy. These vectors are capable of delivering nucleic acid containing constructs which result in the production of full-length therapeutic levels of biologically active Factor VIII in the recipient individual in vivo. The present invention also provides pharmaceutical compositions comprising such AAV vectors, as well as methods for making and using these constructs.

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Alameda, CA, United States of America

Peter C Colosi