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.
Type:
Grant
Filed:
September 30, 1996
Date of Patent:
December 30, 2003
Assignees:
National Institutes of Health, University of Pittsburgh
Inventors:
Richard Jude Samulski, Christopher E. Walsh, Arthur W. Nienhuis, Johnson M. Liu, Jeffrey L. Miller
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.
Type:
Grant
Filed:
April 14, 1998
Date of Patent:
April 15, 2003
Assignees:
Cell Genesys, Inc., The University of North Carolina at Chapel Hill
Inventors:
Richard Jude Samulski, Xiao Xiao, Richard Snyder
Abstract: Homologous recombination is employed to inactivate genes, particularly genes associated with MHC antigens. Particularly, each of the .beta..sub.2- microglobulin gene and the IFN-.gamma.R gene is inactivated for reducing or eliminating the expression of functional MHC antigens. The resulting cells may be used as universal donor cells. In addition, embryonic stem cells may be modified by homologous recombination for use in producing chimeric or transgenic mammalian hosts, which may be used as source of universal donor organs, or as models for drug and transplantation therapies. Methods for homologous recombination in non-transformed mammalian somatic cells are also described.
Type:
Grant
Filed:
December 30, 1993
Date of Patent:
November 12, 1996
Assignee:
Cell Genesys
Inventors:
Raju Kucherlapati, Beverly H. Koller, Oliver Smithies, Robert B. Dubridge, Gary Greenburg, Daniel J. Capon, Steven R. Williams, Mariona L. A. De Rafael