Research Corporation Technologies, Inc.

Other

Advanced Research & Technology Institute

Arun Srivastava

Xu-Shan Wang

Selvarangan Ponnazhagan

Jaime A Escobedo

Mervin C Yoder

Varavani J Dwarki

Shang-Zhen Zhou

Robert H Chloemer

Keyun Qing

Anil Bajpai

The present invention identifies a protein, designated the D-sequence-binding protein (D-BP), is phosphorylated at tyrosine residues and blocks AAV-mediated transgene expression in infected cells by inhibiting the leading strand viral DNA synthesis. More particularly, the present invention demonstrates that D-BP is phosphorylated by EGF-R protein tyrosine kinase. Methods of increasing transcription and promoting replication of transgenes exploiting this information are disclosed herein.

Role of tyrosine phosphorylation of a cellular protein in adeno-associated virus 2-mediated transgene expression

The present invention is directed to a recombinant adenovirus vector comprising two inverted terminal repeats (ITRs) each of which comprises a D-sequence having (i) from 5 to 15 native nucleotides and (ii) one or more deletions or substitutions therein.

AAV vectors

Gene therapy involves the transfer and stable insertion of new genetic information into cells. The present invention is directed to safe vectors for gene therapy and thus provides hybrid parvovirus vectors which are capable of site-specific integration into a mammalian chromosome without substantial cytotoxicity, and which direct erythroid cell-specific expression of heterologous genes. The hybrid vector is useful in gene therapy, particularly in the treatment of hemoglobinopathies and other hematopoietic diseases, and in conferring cell-specific multidrug resistance. A method of delivery of constitutive levels of a pharmaceutical product and a method of producing a recombinant protein are also provided.

Vector for gene therapy

Gene therapy involves the transfer and stable insertion of new genetic information into cells. The present invention is directed to safe vectors for gene therapy and thus provides hybrid parvovirus vectors which are capable of site-specific integration into a mammalian chromosome without substantial cytotoxicity, and which direct erythroid cell-specific expression of heterologous genes. The hybrid vector is useful in gene therapy, particularly in the treatment of hemoglobinopathies and other hematopoietic diseases. A method of delivery of constitutive levels of a pharmaceutical product and a method of producing a recombinant protein are also provided.

Safe vector for gene therapy

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Indianapolis, IN, United States of America

Arun Srivastava