Abstract: An adenoviral vector including at least one DNA sequence encoding a clotting factor, such as, for example, Factor VIII, or Factor IX. Such vectors may be administered to a host in an amount effective to treat hemophilia in the host. The vectors infect hepatocytes very efficiently, whereby the hepatocytes express the DNA sequence encoding the clotting factor.

Abstract: Disclosed are methods and compositions for treatment of diabetes, obesity and diabetic-related conditions. The methods include gene therapy based administration of a therapeutically effective amount of vectors encoding the following: glucokinase regulatory protein alone or co-administered with glucokinase or with metabolism modifying proteins; glucokinase co-administered with metabolism modifying proteins; or glucokinase regulatory protein co-administered with glucokinase in combination with metabolism modifying proteins, to a diabetic patient. Wherein the metabolism modifying proteins include UCP2, UCP3, PPAR&agr;, OB-Rb, GLP-1 and GLP-1 analogs (administered via vector or directly as a peptide). Preferred examples of GLP-1 analogs include GLP-1-Gly8, Extendin-4 and the “Black Widow” chimeric GLP-1 analog. Additionally, PPAR&agr; ligands and DPP-IV inhibitors may be co-administered with the above.

Abstract: The present invention provides novel viral vectors and methods useful for the minimization of leaky gene expression, and, in particular, of nonspecific transcriptional read-through of genes. Such constructs may be obtained by the insertion of an insulating sequence into a vector construct, such as for example a termination signal sequence upstream of the transcription initiation site of the respective transcription unit.

Abstract: The present invention relates to oncolytic adenoviral vectors and their use in methods of gene therapy. Provided is a recombinant viral vector comprising an adenoviral nucleic acid backbone, wherein said nucleic acid backbone comprises in sequential order: A left ITR, a termination signal sequence, an E2F responsive promoter which is operably linked to a gene essential for replication of the recombinant viral vector, an adenoviral packaging signal, and a right ITR.

Abstract: The present invention provides novel lentiviral packaging constructs that are useful for the establishment of stable packaging cell lines and producer cell lines. In particular, the present invention provides novel packaging cell lines that are capable of constitutively expressing high levels of lentiviral proteins.

Abstract: This invention relates to mutated adenoviral fiber proteins and adenovirus particles containing such proteins. It further relates to polynucleotides encoding the proteins and vectors containing polynucleotides. It also relates to methods for making and using the adenoviral particles. With the mutated fiber proteins, the adenovirus particles no longer bind to their natural cellular receptor. They can then be “retargeted” to a specific cell type through the addition of a ligand to the virus capsid, which causes the virus to bind to and infect such cell. Specific fiber mutations are listed, which ablate binding to the natural receptor. Adenovirus particles with certain fiber mutations were found to enhance gene transfer to and expression in liver as compared to viral particles with wild-type fiber.

Abstract: The present invention relates to targeting molecules which are useful to specifically target an adenoviral particle to a desired cell type. These targeting molecules comprise a soluble adenoviral receptor domain, a trimerization domain, and a targeting ligand domain. Further provided are polynucleotides encoding such targeting molecule, expression vectors including such polynucleotides, and methods to target an adenoviral particle to a cell, as well as methods to deliver a heterologous gene selectively to a cell.

Abstract: This invention pertains to BIV constructs encompassing BIV combination vectors, BIV vectors and BIV packaging vectors and particularly the invention pertains to a three vector system comprising: a) a BIV vector construct including a DNA segment from a BIV genome, a packaging sequence to package RNA into virions; a promoter operably linked to the DNA segment; and a transgene operably linked to a second promoter; b) a BIV packaging vector construct comprising a BIV DNA sequence fragment comprising at least a gag gene or pol gene of BIV; a promoter operably linked to the BIV DNA fragment; and a polyadenylation sequence located downstream of the BIV DNA fragment; and c) an expression vector construct comprising a gene encoding a viral surface protein. Also provided is a method for transferring a gene of interest into a mammalian cell.

Abstract: An adenoviral vector including at least one DNA sequence encoding a clotting factor, such as, for example, Factor VIII, or Factor IX. Such vectors may be administered to a host in an amount effective to treat hemophilia in the host. The vectors infect hepatocytes very efficiently, whereby the hepatocytes express the DNA sequence encoding the clotting factor.

Abstract: Disclosed are methods and compositions for treatment of diabetes, obesity and diabetic-related conditions. The methods include gene therapy based administration of a therapeutically effective amount of vectors encoding the following: glucokinase regulatory protein alone or co-administered with glucokinase or with metabolism modifying proteins; glucokinase co-administered with metabolism modifying proteins; or glucokinase regulatory protein co-administered with glucokinase in combination with metabolism modifying proteins, to a diabetic patient. Wherein the metabolism modifying proteins include UCP2, UCP3, PPAR&agr;, OB-Rb, GLP-1 and GLP-1 analogs (administered via vector or directly as a peptide). Preferred examples of GLP-1 analogs include GLP-1-Gly8, Extendin-4 and the “Black Widow” chimeric GLP-1 analog. Additionally, PPAR&agr; ligands and DPP-IV inhibitors may be co-administered with the above.

Abstract: A method for generating adenoviral vectors from polynucleotides such as plasmids wherein there occurs recombinase-mediated transfer of an adenoviral ITR and terminal proteins bound to the ITR to a plasmid, thus enabling the plasmid to replicate as an adenoviral vector. Such method enables the rapid generation of adenoviral vectors at high titers from plasmids without the use of selectable markers and screening procedures. Such method enables the rapid generation of adenoviral vectors devoid of adenovirus backbone genes. The method also may be employed to generate hybrid adenoviral-retroviral vectors that convert transduced cells into producer cells that produce retroviral vectors to effect high level, permanent genetic modification of cells in vivo.

Abstract: An adenoviral vector including at least one DNA sequence encoding a clotting factor, such as, for example, Factor VIII, or Factor IX. Such vectors may be administered to a host in an amount effective to treat hemophilia in the host. The vectors infect hepatocytes very efficiently, whereby the hepatocytes express the DNA sequence encoding the clotting factor.