Genzyme Corporation

Canji Inc.

University of California

Richard J Gregory

Donna Armentano

Alan E Smith

Daniel C Maneval

Ken N Wills

Seng H Cheng

John Marshall

Larry A Couture

Johanne Kaplan

Douglas Antelman

Kenneth N Wills

H Michael Shepard

Karen Vincent

Craig S Siegel

David J Harris

Edward R Lee

Abraham Scaria

Samuel C Wadsworth

Wen-Hwa Lee

Ronald K Scheule

Nelson S Yew

Simon J Eastman

Chau-Dung Chang

Rebecca G Bagley

Eva Y-hp Lee

S Catherine Hubbard

Kathleen M Hehir

Sucharita Paul

David Goodrich

Nan-Ping Wang

Duane E Johnson

Patrick W Rafter

Gene Therapy vectors, which are especially useful for cystic fibrosis, and methods for using the vectors are disclosed.

Adenovirus vectors for gene therapy

Disclosed are full length isolated DNAs encoding cystic fibrosis transmembrane conductance regulator (CFTR) protein and a variety of mutants thereof. Also disclosed are antibodies specific for various CFTR domains and methods for their production. Expression of CFTR from cells transformed with these CFTR genes or cDNAs demonstrate surprising CFTR intracellular distributions and results thereby providing for new diagnostic and therapeutic procedures.

DNA molecules stabilized for propagation in bacterial cells that encode cystic fibrosis transmembrane conductance regulator

Disclosed are methods of controlling cell cycle progression by introducing into a cell to be controlled a composition selected from the group consisting of p56protein, a fragment of the p56protein, and the gene encoding p56protein to alter the cell cycle progression while maintaining the viability of the cell. The p56protein has been found to have the unexpected and surprising characteristic of being soluble in low concentrations of glycerol, thereby enhancing its value in pharmaceutical applications and the gene encoding p56when delivered to the hyperproliferating cell inhibits cellular proliferation.

Method of using an adenoviral vector encoding a retinoblastoma protein to treat hyperproliferating cells

The present invention provides recombinant nucleic acid molecules encoding a chimeric transactivator protein including a DNA binding domain of a DNA binding protein and a protein domain capable of transcriptional activation. The present invention also provides recombinant viral and non-viral vectors that are able to infect and/or transfect and sustain expression of a biologically active chimeric transactivator proteins in mammalian cells. Also provided are host cell lines and non-human transgenic animals capable of expressing biologically active chimeric transactivator proteins. In another aspect, compositions and methods for treating or preventing ischemic damage associated with hypoxia-related disorders are provided.

Compositions and methods for inducing gene expression

This invention provides a recombinant adenovirus expression vector characterized by the partial or total deletion of the adenoviral protein IX DNA and having a gene encoding a foreign protein or a functional fragment or mutant thereof. Transformed host cells and a method of producing recombinant proteins and gene therapy also are included within the scope of this invention. Thus, for example, the adenoviral vector of this invention can contain a foreign gene for the expression of a protein effective in regulating the cell cycle, such as p53, Rb, or mitosin, or in inducing cell death, such as the conditional suicide gene thymidine dinase. (The latter must be used in conjunction with a thymidine kinase metabolite in order to be effective.)

Recombinant adenoviral vector and method of use

This invention provides a recombinant adenovirus expression vector characterized by the partial or total deletion of the adenoviral protein IX DNA and having a gene encoding a foreign protein or a functional fragment or mutant thereof. Transformed host cells and a method of producing recombinant proteins and gene therapy also are included within the scope of this invention. Thus, for example, the adenoviral vector of this invention can contain a foreign gene for the expression of a protein effective in regulating the cell cycle, such as p53, Rb, or mitosin, or in inducing cell death, such as the conditional suicide gene thymidine kinase. (The latter must be used in conjunction with thymidine kinase metabolite in order to be effective).

Recombinant adenoviral vector and methods of use

Fusions of the transcription factor E2F and the retinoblastoma protein RB are provided, along with methods of treatment of hyperproliferative diseases.

Methods of treating hyperproliferative disorders using retinoblastoma fusion proteins

The present invention relates to transgene expression systems, related compositions comprising the transgene expression systems, and methods of making and using them. Preferred systems employ an adenovirus transgene expression vector comprising DNA encoding a transgene which codes for a desired product operably linked to expression control sequence, and at least a portion of the adenovirus E3 region and certain portions of the E4 region. The E4 portions comprise the open reading frame sequence known as E4ORF3 and at least one other portion of E4. Preferably the E4 portion of the vector (or &ldquo;E4 cassette&rdquo;) includes E4ORF3 and at least one other portion selected from E4ORF4, E4ORF6/7 and E4ORF3/4. The invention has a number of important features including improving persistency of transgene expression in a desired host cell. The transgene expression systems of the present invention are useful for a variety of applications including providing persistent cellular expression of the transgene in vitro and in vivo.

Transgene expression systems

Retinoblastoma fusion proteins

The present invention relates to transgene expression systems, related compositions comprising the transgene expression systems, and methods of making and using them. Preferred systems employ an adenovirus transgene expression vector comprising DNA encoding a transgene which codes for a desired product operably linked to expression control sequence, and at least a portion of the adenovirus E3 region and certain portions of the E4 region. The E4 portions comprise the open reading frame sequence known as E40RF3 and at least one other portion of E4. Preferably the E4 portion of the vector (or &ldquo;E4 cassette&rdquo;) includes E40RF3 and at least one other portion selected from E40RF4, E40RF6/7 and E40RF3/4. The invention has a number of important features including improving persistency of transgene expression in a desired host cell. The transgene expression systems of the present invention are useful for a variety of applications including providing persistent cellular expression of the transgene in vitro and in vivo.

Novel cationic amphiphiles are provided that facilitate transport of biologically active (therapeutic) molecules into cells. The amphiphiles contain lipophilic groups derived from steroids, from mono or dialkylamines, or from alkyl or acyl groups; and cationic groups, protonatable at physiological pH, derived from amines, alkylamines or polyalkylamines. There are provided also therapeutic compositions prepared typically by contacting a dispersion of one or more cationic amphiphiles with the therapeutic molecules. Therapeutic molecules that can be delivered into cells according to the practice of the invention include DNA, RNA, and polypeptides. Representative uses of the therapeutic compositions of the invention include providing gene therapy, and delivery of antisense polynucleotides or biologically active polypeptides to cells. With respect to therapeutic compositions for gene therapy, the DNA is provided typically in the form of a plasmid for complexing with the cationic amphiphile. Novel and highly effective plasmid constructs are also disclosed, including those that are particularly effective at providing gene therapy for clinical conditions complicated by inflammation. Additionally, targeting of organs for gene therapy by intravenous administration of therapeutic compositions is described.

Organ-specific targeting of cationic amphiphile / DNA complexes for gene therapy

This invention provides a recombinant adenovirus expression vector characterized by the partial or total deletion of the adenoviral protein IX DNA and having a gene encoding a foreign protein or a functional fragment or mutant thereof. Transformed host cells and a method of producing recombinant proteins and gene therapy also are included within the scope of this invention. Thus, for example, the adenoviral vector of this invention can contain a foreign gene for the expression of a protein effective in regulating the cell cycle, such as p53, Rb, or mitosin, or in inducing cell death, such as the conditional suicide gene thymidine kinase. (The latter must be used in conjunction with a thymidine kinase metabolite in order to be effective).

The present invention relates to transgene expression systems, related pharmaceutical compositions, and methods of making and using them. Preferred systems employ an adenovirus transgene expression vector comprising DNA sequence encoding a transgene which codes for a desired product, expressibly contained within an adenovirus vector containing at least a portion of the E3 region and certain portions of the E4 region. The E4 portions comprise the open reading frame sequence known as E4ORF3 and at least one other portion of E4. Preferably the E4 portion of the vector (or 'E4 cassette') includes E4ORF3 and at least one other portion selected from E4ORF4, E4ORF6/7 and E4ORF3/4. The invention has a number of important features including improving persistency of transgene expression in a desired host cell. The transgene expression systems of the present invention are useful for a variety of applications including providing persistent cellular expression of the transgene in vitro and in vivo.

Growing community of inventors

Carlsbad, CA, United States of America

Richard J Gregory