University of Washington

Compliment Corporation

Andre Lieber

Mark A Kay

Darrick Carter

Ronald Jay Berenson

Hongjie Wang

Desmoglein 2 (DSG2) Binding Proteins and Uses Therefor

The present invention provides recombinant adenoviral compositions and methods for their use in treating disorders associated with epithelial tissues.

Desmoglein 2 (DSG2) binding proteins and uses therefor

The present invention provides compositions, compounds, and methods relating to recombinant adenoviral-based polypeptides for treating disorders associated with epithelial tissues.

Methods and systems for adenovirus interaction with desmoglein 2 (DSG2)

The invention provides compositions of a non-adenoviral vector containing a polynucleotide sequence encoding adenoviral pTP operationally linked domain. The invention also provides compositions of an adenoviral pTP binding domain. The invention also provides methods for increasing the expression of a polynucleotide by expressing the polynucleotide in a non-adenoviral vector containing an adenoviral pTP binding domain in the presence of adenoviral pTP. The invention additionally provides methods to increase expression of a heterologous polynucleotide in an individual by obtaining cells from the individual, genetically altering the cells to express a non-adenoviral vector containing an adenoviral pTP binding domain and a gene encoding pTP and readministering the genetically altered cells to the individual.

Methods and compositions for enhanced stability of non-adenoviral DNA

Adenoviral vectors are used for high efficiency transduction of ribozymes specific for hepatitis C virus RNA. Hepatocytes are transduced with a recombinant adenovirus vector that expresses a ribozyme capable of specifically cleaving HCV RNA. The compositions and methods thus provide new means for treating HCV, and further provide transgenic non-human animals having human hepatocytes which are useful in models of HCV disease for developing therapeutic and preventative agents.

Ribozymes for treating hepatitis C

A method of inhibiting hepatitis C virus RNA replication or expression is provided. The method consists of introducing two or more ribozymes specific for hepatitis C virus RNA into a cell infected with hepatitis C virus. The ribozymes specific for hepatitis C virus RNA can specifically cleave hepatitis C RNA in a HCV 5' non-coding sequence, the capsid sequence, the NS-5 sequence or any other conserved region of the hepatitis C RNA. The ribozymes can also be selected so as to be specific for opposite strands of the virus genome. A method of inhibiting hepatitis C virus RNA replication or expression is also provided which consists of introducing into a cell infected with hepatitis C virus at least one ribozyme specific for hepatitis C virus which is selected from the group consisting of GGGAGGTCTCGTAGA [SEQ ID NO: 1], GCACCATGAGCACGA [SEQ ID NO: 2], CCCACAGGACGTCAA [SEQ ID NO: 3], CAACCGTCGCCCACA [SEQ ID NO: 4], TAAACCTCAAAGAAA [SEQ ID NO: 5] GTAAGGTCATCGATA [SEQ ID NO: 6]. Compositions consisting of two or more ribozymes specific for hepatitis C virus RNA is also provided.

A combination of retroviral and adenoviral vectors are used for high efficiency gene transfer into hepatocytes, resulting in long term gene expression. Hepatocytes are transduced in vivo with a recombinant adenovirus vector that expresses a molecule capable of inducing hepatocyte regeneration, such as urokinase plasminogen activator (uPA) or tissue plasminogen activator (tPA), resulting in a high rate of liver regeneration. During the regenerative phase, ex vivo or in vivo retroviral-mediated gene transfer into hepatocytes results in greater transduction efficiencies. The compositions and methods thus provide new means for gene therapy, and transgenic non-human animals useful in developing new therapeutic and preventative agents.

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Seattle, WA, United States of America

Andre Lieber