Richard J Samulski

US Patent:

6410300, Jun 25, 2002

Filed:

Jan 11, 1999

Appl. No.:

09/228203

Inventors:

Richard Jude Samulski - Chapel Hill NC
Candace Summerford - Chapel Hill NC

Assignee:

The University of North Carolina at Chapel Hill - Chapel Hill NC

International Classification:

C12N 700

US Classification:

435239, 4352351, 4353201, 435 5, 424 932

Abstract:

Primary receptors and co-receptors for adeno-associated virus (AAV) attachment to and infection of target cells are described. Such receptors can be used to facilitate AAV attachment to and infection of cells, e. g. , for gene therapy. Methods for purification and/or concentration of AAV are also described. Methods of facilitating or enhancing AAV infection of a cell are also provided. Also described are methods of inhibiting or preventing infection of AAV into a cell. Cell samples may be screened for permissiveness for AAV attachment and infection by detecting the presence or abundance of cellular receptors that mediate attachment and/or infection of AAV into the cell. Formulations and kits for mediating AAV attachment to, and infection of, cells are also provided herein.

US Patent:

6458587, Oct 1, 2002

Filed:

Mar 21, 2001

Appl. No.:

09/813041

Inventors:

Forrest K. Ferrari - Chapel Hill NC
Xiao Xiao - Chapel Hill NC
Richard Jude Samulski - Chapel Hill NC

Assignee:

The University of North Carolina at Chapel Hill - Chapel Hill NC

International Classification:

C12N 15864

US Classification:

435369, 4353201, 435325, 435366, 4352351

Abstract:

A method for the production of adeno-associated virus stocks and recombinant adeno-associated virus stocks that are substantially free of contaminating helper virus is described. The method utilizes transfection with helper virus vectors to replace the infection with helper virus used in the conventional method.

US Patent:

6491907, Dec 10, 2002

Filed:

Nov 10, 1999

Appl. No.:

09/438268

Inventors:

Joseph E. Rabinowitz - Carrboro NC
Richard Jude Samulski - Chapel Hill NC
Weidong Xiao - Jenkintown PA

Assignee:

The University of North Carolina at Chapel Hill - Chapel Hill NC

International Classification:

A61B 5055

US Classification:

424 932, 424 931, 424 9321, 424 933, 424 936

Abstract:

The present invention provides genetically-engineered parvovirus capsids and viruses designed to introduce a heterologous gene into a target cell. The parvoviruses of the invention provide a repertoire of vectors with altered antigenic properties, packaging capabilities, and/or cellular tropisms as compared with current AAV vectors.

US Patent:

6548286, Apr 15, 2003

Filed:

Apr 14, 1998

Appl. No.:

09/060102

Inventors:

Richard Jude Samulski - Chapel Hill NC
Xiao Xiao - Wexford PA
Richard Snyder - Oakland CA

Assignee:

Cell Genesys, Inc. - Foster City CA
The University of North Carolina at Chapel Hill - Chapel Hill NC

International Classification:

C12N 701

US Classification:

4352351, 435369

Abstract:

The present invention relates to methods and compositions for increasing the production of high titre stocks of recombinant AAV (rAAV) through regulation of expression of the AAV REP and CAP proteins. The methods and compositions of the invention are based on the observation that the low level expression of the AAV REP protein increases the production of AAV viral capsid protein and efficiency of packaging resulting in production of higher titre recombinant viral stocks. The invention encompasses recombinant AAV vectors that direct the expression of AAV REP and CAP proteins and the use of such vectors for the production of novel stable cell lines capable of generating high titre rAAV vectors. The invention provides methods for regulating the expression of the AAV REP gene at the transcriptional and post-translational level. The methods and compositions of the invention can be used to produce high titre stocks of rAAV which can be used in gene therapy for the purpose of transferring genetic information into appropriate host cells for the management and correction of human diseases including inherited and acquired disorders.

US Patent:

6627617, Sep 30, 2003

Filed:

Sep 29, 2000

Appl. No.:

09/676726

Inventors:

Richard Jude Samulski - Chapel Hill NC
Denise Gavin - Silver Spring MD
Nicholas Muzyczka - Gainesville FL
Corinne Abernathy - Gainesville FL
Daniel Pereira - Alexandria VA

Assignee:

University of North Carolina at Chapel Hill - Chapel Hill NC

International Classification:

C12N 1563

US Classification:

514 44, 4242331, 4353201, 4352351, 435325

Abstract:

The present invention provides temperature-sensitive (ts) adeno-associated virus (AAV) Rep78 and Rep68 proteins. In preferred embodiments, the ts AAV Rep78 and Rep68 proteins have missense mutations at amino acid positions 40, 42 and 44 that confer a temperature-sensitive phenotype. Also provided are nucleotide sequences and vectors encoding the inventive ts Rep proteins. In preferred embodiments, a hybrid adenovirus vector is provided that stably comprises a nucleotide sequence encoding a ts AAV Rep protein according to the invention. The present invention also provides methods of packaging AAV vectors and methods of ex vivo gene delivery using the ts Rep proteins of the invention. Further provided are cells containing the ts AAV Rep proteins, preferably stably integrated into the genome of the cell.

US Patent:

6670176, Dec 30, 2003

Filed:

Sep 30, 1996

Appl. No.:

08/723303

Inventors:

Richard Jude Samulski - Chapel Hill NC
Christopher E. Walsh - Bethesda MD
Arthur W. Nienhuis - Memphis TN
Johnson M. Liu - Rockville MD
Jeffrey L. Miller - Laurel MD

Assignee:

National Institutes of Health - Rockville MD
University of Pittsburgh - Pittsburgh PA

International Classification:

C12N 1574

US Classification:

4353201, 435325, 435455, 435457, 4352351, 435236, 435456, 514 44, 424 932, 424 9321

Abstract:

The subject invention concerns a recombinant adeno-associated virus vector characterized as being capable of delivering and expressing at least one mammalian gene into a genome of a mammalian host cell such that the expression of the gene is regulated in a tissue specific manner by cis-acting regulatory and promoter elements of the gene. A method of using this recombinant adeno-associated virus vector for therapeutic purposes is also provided.

US Patent:

6703237, Mar 9, 2004

Filed:

Mar 20, 2002

Appl. No.:

10/102314

Inventors:

Richard Jude Samulski - Chapel Hill NC
Candace Summerford - Chapel Hill NC

Assignee:

University of North Carolina at Chapel Hill - Chapel Hill NC

International Classification:

C12N 15864

US Classification:

4353201, 435455, 435456

Abstract:

Primary receptors and co-receptors for adeno-associated virus (AAV) attachment to and infection of target cells are described. Such receptors can be used to facilitate AAV attachment to and infection of cells, e. g. , for gene therapy. Methods for purification and/or concentration of AAV are also described. Methods of facilitating or enhancing AAV infection of a cell are also provided. Also described are methods of inhibiting or preventing infection of AAV into a cell. Cell samples may be screened for permissiveness for AAV attachment and infection by detecting the presence or abundance of cellular receptors that mediate attachment and/or infection of AAV into the cell. Formulations and kits for mediating AAV attachment to, and infection of, cells are also provided herein.

US Patent:

6951758, Oct 4, 2005

Filed:

Jul 13, 2004

Appl. No.:

10/889105

Inventors:

Forrest K. Ferrari - Chapel Hill NC, US
Xiao Xiao - Chapel Hill NC, US
Richard Jude Samulski - Chapel Hill NC, US

Assignee:

The University of North Carolina at Chapel Hill - Chapel Hill NC

International Classification:

C12N005/10
C12N015/861
C12N015/63
C12N015/64

US Classification:

435457, 4353201, 435455, 435456, 4352351, 435325, 435366, 435369

Abstract:

A method for the production of adeno-associated virus stocks and recombinant adeno-associated virus stocks that are substantially free of contaminating helper virus is described. The method utilizes transfection with helper virus vectors to replace the infection with helper virus used in the conventional method.