National Research Council of Canada

Other

Centre De Recherche Du Centre Hospitalier De L'universit&eacute; De Montr&eacute;al

The Royal Institution for the Advancement of Learning / Mcgill University

Universitéde Montreal

Bernard Massie

Traian Sulea

Alaka Mullick

Danica Stanimirovic

Mehdi Arbabi-Ghahroudi

Kristin Kemmerich

Arsalan S Haqqani

Rénald Gilbert

Wahiba Oualikene

Peter C K Lau

Yasuo Konishi

Carlos B Miguez

Yves Langelier

Amine A Kamen

Renald Gilbert

Young-Jun Choi

Yan Xu

Natalie Lamarche

M T Johanne C&ocirc;t&eacute;

Seyyed Mehdy Elahi

Young Jun Choi

Marilyne Blain

Pnina Brodt

Peter Ck Lau

There are described herein novel soluble IGF receptor Fc fusion proteins and compositions and methods of use thereof for treating angiogenesis associated disorders and malignant disease, such as cancer and metastasis, wherein the fusion proteins bind specifically to IGF-1 or IGF-2.

Soluble IGF receptor Fc fusion proteins and uses thereof

The blood-brain barrier (BBB) prevents transport of molecules larger than 500 Dal tons from blood to brain. Receptor-mediated transcytosis (RMT) facilitates transport across the BBB of specific molecules that bind receptors on brain endothelial cells that form the BBB. An insulin-like growth factor 1 receptor (IGF 1R)-binding antibody or fragment thereof is identified that transmigrates the BBB by RMT. The antibody or fragment is used to deliver a cargo molecule across the BBB, wherein the cargo molecule may be a therapeutic or detectable agent. The antibody is a camelid VHH, prepared by immunizing a llama with a 933-amino acid IGF 1R polypeptide. Humanized forms of the camelid VHH are also generated.

Insulin-like growth factor 1 receptor-specific antibodies and uses thereof

The blood-brain barrier (BBB) prevents transport of molecules larger than 500 Daltons from blood to brain. Receptor-mediated transcytosis (RMT) facilitates transport across the BBB of specific molecules that bind receptors on brain endothelial cells that form the BBB. An insulin-like growth factor 1 receptor (IGF1R)-binding antibody or fragment thereof is identified that transmigrates the BBB by RMT. The antibody or fragment is used to deliver a cargo molecule across the BBB, wherein the cargo molecule may be a therapeutic or detectable agent. The antibody is a camelid VHH, prepared by immunizing a llama with a 933-amino acid IGF1R polypeptide. Humanized forms of the camelid VHH are also generated.

Efficient and muscle-specific gene expression can be obtained with constructs containing two or more copies of USE and/or &#x394;USE fused to the minimal promoter of the TnISlow gene. USE is a small (about 160-bp) upstream enhancer of the TnISlow gene that confers slow-twitch muscle fiber specificity. &#x394;USE is generated from a 100-bp deletion at the 5' end of USE. &#x394;USE confers expression in slow- and fast-twitch muscle fibers. The strength and relatively small size (less than 600-bp) of these constructs make them useful for gene therapy applications.

Constructs for enhancement of gene expression in muscle

Recently, the development of inducible expression systems has involved exploitation of the p-cym operon from. Disclosed herein are novel expression systems and components thereof, which involve the development of CymR variants with reverse DNA binding activity, such that they exhibit increased affinity for DNA in a presence rather than an absence of an effector molecule such as cumene or an equivalent thereof. Also disclosed are the CymR variants, fusion proteins incorporating such variants, and their use in the control and expression of polynucleotides.

Reverse cumate repressor mutant

An expression system for transforming E coll with a nucleic acid molecule of interest has an operator sequence of a cmt operon operatively linked to a promoter for the operator, and, a repressor sequence from a cym operon operatively linked to a promoter for the repressor. The expression system may have a nucleic acid molecule of interest, for example, a nucleic acid molecule that encodes a protein. Any type of E coll host cells may be transformed with the expression system. A method of producing a protein involves transforming an E coll host cell with the expression system having a nucleic acid molecule that codes for a protein, and, culturing the host cell in a culture medium under conditions in which the nucleic acid molecule will express the protein.

Inducible/regulated gene expression system in E coli

Methylotrophic or methanotrophic bacteria such asare transformed with a gene of interest, and expression of the gene is regulated by means of a cumate repressor protein and an operator sequence which is operatively linked to the gene of interest, and the addition of an external agent. Specifically, the cymR repressor and cmt operator frommay serve to regulate gene expression in methylotrophic or methanotrophic bacteria with the addition of cumate.

Regulation of heterologous recombinant protein expression in methylotrophic and methanotrophic bacteria

The invention relates to a new 'gene-switch' (cumate-inducible switch) for mammalian cells, having a mammalian promoter which has a TATA element and is linked to the coding sequence of CymR. This switch is as useful in the development of expression systems and cell-based assays for functional genomics as in the generation of viral vectors for gene therapy.

DNA for eukaryotic expression of CymR

The invention relates to a new 'gene-switch' (cumate-inducible switch) for mammalian cells. This switch is as useful in the development of expression systems and cell-based assays for functional genomics as in the generation of viral vectors for gene therapy.

Cumate-inducible expression system for eukaryotic cells

Disclosed is a new system for generating recombinant adenovirus vectors and adenovirus-based expression libraries, by positive selection of recombinants deleted for the endogenous protease gene, which gene is expressibly cloned into another region of the adenoviral genome. In a preferred embodiment, the invention allows positive selection of E1-deleted, protease-deleted recombinant adenovirus vectors comprising an exogenous gene or an expressible piece of exogenous DNA, by providing an expression cassette comprising the protease gene and the exogenous DNA inserted in place of E1 region in a shuttle vector. In vivo recombination of the shuttle vector with a protease-deleted adenoviral genome in suitable non-complementing cells generates viable recombinants only when rescuing the protease cloned in E1 region. Non-recombinant viral genomes are not able to grow due to the deletion of the protease gene, ensuring that only recombinant viral plaques are generated. This positive selection can be used for the generation of a large number of high purity recombinant adenovirus vectors and allows generation of adenovirus-based libraries with diversity exceeding 10 clones.

Efficient generation of adenovirus-based libraries by positive selection of adenoviral recombinants through ectopic expression of the adenovirus protease

An adenovirus vector/packaging cell line system is disclosed, in which the vector replication is blocked by deletion of a single gene, which deletion does not interfere with any other viral functions. The deleted gene is the gene of the adenovirus protease. The protease is expressed in a complementing (packaging) cell line through a regulatable expression cassette which induces no toxic effects in the cells, thus making the generation and propagation of the vector easier and more efficient. As the deleted gene is highly specific of adenovirus, no complementation of the gene in transduced cells is expected, which increases the safety of the new vectors for gene transfer purposes. Also disclosed is a new system of generating recombinant adenovirus vectors by positive selection of recombinants deleted for the endogenous protease gene, which gene is cloned in another region of the adenoviral genome.

Complementary cell line for the growth of adenovirus mutants with a deleted protease gene

An anti-apoptotic agent and a composition derived therefrom, and methods to prevent apoptosis in vivo and in vitro are provided. The anti-apoptotic agent comprises R1 subunit of Herpes simplex virus (HSV) ribonucleotide reductase, or its N-terminal portion of about 350 amino acids. HSV-R1 inhibited TNF-&agr; induced apoptosis, and blocked caspase 8 activation induced by TNF-&agr; and Fas-L expression.

Anti-apoptotic compositions comprising the R1 subunit of herpes simplex virus ribonucleotide reductase or its N-terminal portion; and uses thereof

Adenovirus mutants with deleted protease gene

The present invention relates to a method of serum-free production of recombinant proteins and adenoviral vectors; cell lines viable in a serum-free medium and method of obtaining same.

Growing community of inventors

Laval, Canada

Bernard Massie