Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: Efficient and muscle-specific gene expression can be obtained with constructs containing two or more copies of USE and/or ?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. ?USE is generated from a 100-bp deletion at the 5? end of USE. ?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.

Abstract: 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.

Abstract: Recently, the development of inducible expression systems has involved exploitation of the p-cym operon from Pseudomonas putida. 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.

Abstract: 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.

Abstract: Efficient and muscle-specific gene expression can be obtained with constructs containing two or more copies of USE and/or ?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. ?USE is generated from a 100-bp deletion at the 5? end of USE. ?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.

Abstract: Methylotrophic or methanotrophic bacteria such as Methylobacterium are 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 from Pseudomonas putida may serve to regulate gene expression in methylotrophic or methanotrophic bacteria with the addition of cumate.

Abstract: 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.

Abstract: Methylotrophic or methanotrophic bacteria such as Methylobacterium are 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 from Pseudomonas putida may serve to regulate gene expression in methylotrophic or methanotrophic bacteria with the addition of cumate.

Abstract: 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.

Abstract: 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.

Abstract: An expression system for transforming E. coli 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. coli host cells may be transformed with the expression system. A method of producing a protein involves transforming an E. coli 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.

Abstract: Recently, the development of inducible expression systems has involved exploitation of the p-cym operon from Pseudomonas putido. 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.

Abstract: A baculovirus-based expression system under control of CR5 promoter improves expression of transgenic nucleic acid molecules in mammalian cells. It also provides a platform for regulated expression of transgenic nucleic acid molecules in mammalian cells.