Introgen Therapeutics Inc.

The University of Texas System

Baylor College of Medicine

Introgen Research Institute, Inc.

Deborah R Wilson

Shuyuan Zhang

Zheng Wu

Toohyon Cho

Capucine Thwin

Lucetta Caston

Jack A Roth

James R Smith

David J Drutz

Tomoyuki Saeki

Margaret Wilde

Gretchen J Darlington

Louis A Zumstein

Mary Lapadat-Tapolsky

Julia A Lee

Rajagopal Ramesh

Brian D Almond

Therese M Timmons

The present invention relates to non-viral gene therapy methods and compositions for treatment of hyperproliferative disease in humans. More specifically, the invention is directed, in one embodiment, to lipid formulations which form stable liposome structures, capable of efficient in vivo nucleic acid transfer. In other embodiments, methods and compositions are directed to liposome transfer of anti-proliferative nucleic acids, wherein the transfer of the nucleic acids is cell specific via cell specific targeting moieties. The present invention, thus provides non-viral, liposome compositions and methods of gene transfer particularly useful for targeting and treating hyperproliferative disease.

Methods and compositions for non-viral gene therapy for treatment of hyperproliferative diseases

The present invention addresses the need to improve the yields of viral vectors when grown in cell culture systems. In particular, it has been demonstrated that for adenovirus, the use of low-medium perfusion rates in an attached cell culture system provides for improved yields. In other embodiments, the inventors have shown that there is improved Ad-p53 production with cells grown in serum-free conditions, and in particular in serum-free suspension culture. Also important to the increase of yields is the use of detergent lysis. Combination of these aspects of the invention permits purification of virus by a single chromatography step that results in purified virus of the same quality as preparations from double CsCl banding using an ultracentrifuge.

Methods for producing purified adenoviral vectors

The present invention addresses the need to improve the yields of viral vectors when grown in cell culture systems. In particular, it has been demonstrated that for adenovirus, the use of low-medium perfusion rates in an attached cell culture system provides for improved yields. In other embodiments, the inventors have shown that there is improved Ad-p53 production witrh cells grown in serum-free conditions, and in particular in serum-free suspension culture. Also important to the increase of yields is the use of detergent lysis. Combination of these aspects of the invention permits purification of virus by a single chromatography step that results in purified virus of the same quality as preparations from double CsCl banding using an ultracentrifuge.

Method for the production and purification of adenoviral vectors

Purified adenoviral compositions

The use of liposomal formulations, particularly formulations of positively charged and neutral lipids facilitates cellular uptake of SDI molecules. The transcription and/or expression of SDI-1-encoding nucleic acid molecules is facilitated by constructs that contain intervening untranslated regions.

Senscent cell-derived inhibitors of DNA synthesis

The present invention involves the identification of a factor or factors that are anti-proliferative and can be used in the treatment of cancers and other hyperproliferative disease states. The factor or factors are induced from cells follow contact of the cells with viral or plasmid expression vectors. One factor is between about 3 kDa and 300 kDa in size, while another is less than about 3 kDa in size. Both are heat stable and is resistant to both protease and nuclease treatment. Methods for purification and use of the factor also are disclosed.

Inhibition of cell growth by an anti-proliferative factor

A gene sequence that encodes the human CCAAT/enhancer binding protein ('C/EBP'), and recombinant vectors that are capable of mediating the expression of the C/EBP gene are described. The gene sequence and vector can be used in methods of gene therapy to treat cancer and other diseases.

Human C/EBP gene and vectors for its expression

Growing community of inventors

Houston, TX, United States of America

Deborah R Wilson