University of Pittsburgh

Christopher H Evans

Paul David Robbins

Joseph C Glorioso

Axel W Baltzer

Richard Kane

Geethani Bandara

Steven C Ghivizzani

Richard Kang

The present invention relates to a method for treating bone pathologies comprising delivering a viral or non-viral delivery vehicle comprising genetic information (e.g. a transgene) encoding a therapeutic osteoinductive factor to target cells in vivo enabling the cells to produce the osteoinductive factor at the site of the bone pathology. The delivery is achieved by a simplified method which does not require cumbersome ex vivo techniques or additional matrix or scaffolding agents. Such viral and non-viral delivery vehicles of the present invention are derived from the following nonlimiting examples: adenoviruses, adeno-associated viruses, retroviruses, herpes simplex viruses, liposomes, and plasmids. The osteoinductive factors include, but are not limited to, growth factors, cytokines, growth factor inhibitors and cytokine inhibitors.

Viral and non-viral vectors as vehicles for delivering transgenes for treating bone pathologies

Methods for introducing at least one gene encoding a product into at least one target cell of a mammalian host for use in treating the mammalian host are disclosed. These methods include employing recombinant techniques to produce a vector molecule that contains the gene encoding for the product, and infecting the target cells of the mammalian host using the DNA vector molecule. A method to produce an animal model for the study of connective tissue pathology is also disclosed.

Gene transfer for studying and treating a connective tissue of a mammalian host

The subject invention concerns a method of introducing at least one DNA sequence expressing a protein or protein fragment which substantially alleviates articular cartilage defects. This method involves in vitro culture of chondrocytes, transfection of the chondrocytes with a recombinant vector housing the DNA sequence to be expressed, and delivery of the transfected chondrocytes to the damaged cartilage region. This method can also be used in tandem with synovial cell delivery techniques of the present invention. This method is also useful as a model in animal studies regarding joint pathologies.

Cartilage alterations by administering to joints chondrocytes comprising a heterologous polynucleotide

The subject invention concerns a method of introducing at least one gene encoding a product into at least one cell of a connective tissue of a mammalian host for use in treating the mammalian host including employing recombinant techniques to produce a DNA vector molecule which contains the gene encoding for the product and infecting the connective cell of the mammalian host using the DNA vector molecule using the gene coding for the product. A method is provided for introducing at least one gene encoding a product into at least one cell of a connective tissue of a mammalian host employing non-viral methods. A method to produce an animal model for the study of connective tissue pathology is also disclosed. Additionally, this invention provides a method of using in vivo a gene encoding and extracellular interleukin-1 binding domain of an interleukin-1 receptor.

Viral vectors to inhibit leukocyte infiltration or cartilage degradation of joints

Methods for treating a connective tissue disorder by introducing at least one gene encoding a product into at least one target cell of a mammalian host for use in treating the mammalian host are disclosed. These methods include employing recombinant techniques to produce a vector molecule containing the DNA sequence encoding for the product and infecting the target cell of the mammalian host using the vector. The injection can be done in vivo, by directly injecting the vector into the host, or can be done in vitro by transfecting a population of cultured target cells with the vector and transplanting them each into the host. Nonviral means can also be used to introduce the DNA sequence to the host. Administration of more than one gene of interest results in an enhanced therapeutic benefit. Also disclosed is a method for treating a connective tissue disorder by introducing at least one gene encoding a product into at least one target cell of a joint of a host for use in treating multiple joints of the host. Injection of a vector molecule containing the DNA sequence encoding for a product of interest, or non-viral introduction of such a DNA sequence, to one join of a mammalian host results in a therapeutic benefit in that joint as well as other joints in the host

Viral vectors to inhibit leukocyte infiltration or cartilage degradation

Gene transfer for studying and treating a connective tissue of a

The subject invention concerns a method of introducing at least one gene encoding a product into at least one cell of a connective tissue of a mammalian host for use in treating the mammalian host including employing recombinant techniques to produce a DNA vector molecule which contains the gene encoding for the product and infecting the connective cell of the mammalian host using the DNA vector molecule using the gene coding for the product. A method is provided for introducing at least one gene encoding a product into at least one cell of a connective tissue of a mammalian host employing non-viral means. In a specific example, isolated synovial cells were infected with a retrovirus comprising a DNA sequence encoding IRAP and the transfected cells administered to an arthritic joint. A method to produce an animal model for the study of connective tissue pathology is also disclosed. Additionally, this invention provides a method of using in vivo a gene encoding and extracellular interleukin-1 binding domain of an interleukin-1 receptor.

IRAP gene as treatment for arthritis

The present invention relates to methods of therapeutic or prophylactic treatment of connective tissue diseases by systemic or local delivery of a nucleic acid sequence to a mammalian host. Expression of the nucleic acid sequence results in the systemic delivery of a biologically active protein or peptide which acts to antagonize inflammatory, hypertrophic and erosive phenomenon associated with connective tissue disease. Systemic delivery of such gene products results in sustained treatment of connective tissue diseases such as rheumatoid arthritis and systemic lupus erythematosus.

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Pittsburgh, PA, United States of America

Christopher H Evans