William Beaumont Hospital

Michael J Borrelli

Laurace E Townsend

Diane E Maupin

The invention provides compositions and methods for gene therapy using cytolethal distending toxins (CDTs). In a preferred embodiment, a gene therapy vector according to the invention includes a gene encoding a B subunit of a CDT and an antisense oligonucleotide that inhibits a DNA repair mechanism. An inducible promoter is operably linked to the gene and oligonucleotide. Preferably, the promoter is strictly inducible by heat shock.

Methods and compositions for heat activated gene therapy using cytolethal distending toxin

The present invention provides methods and compositions for enhancing the diffusion of therapeutic agents through mammalian tissue. In one embodiment, invention provides methods and compositions useful for enhancing the diffusion of gene therapy vectors through a mammalian tissue of interest. The method comprises delivering the therapeutic agent and a permeabilizer to the tissue of interest. The method may further comprise inducing hyperthermia in the tissue. In one embodiment, a composition in accordance with the present invention comprises a gene therapy vector containing a polynucleotide and a tissue permeabilizer. A method of destroying tissue is also provided. In one embodiment of this aspect of the invention, the method includes delivering a high concentration of tissue permeabilizer to the tissue and may also include inducing hyperthermia in the tissue.

Methods and compositions for enhancing diffusion of therapeutic agents through tissue

An apparatus and method for culturing living endothelial cells is provided. The apparatus comprises a cell growth container, which in a preferred embodiment is a synthetic graft, heat crimped at both ends. The apparatus further comprises a rotation container that may contain the cell growth container and is attached to a rotation apparatus. The apparatus further comprises fixturing apparatus, which in a preferred embodiment is a pair of o-ring members, that enhances a separated condition of the cell growth container within the rotation container. The method of the present invention comprises providing a culture that includes living cells and a growth medium, introducing the culture into a cell growth container, heat crimping the cell growth container to substantially seal the cell growth container, and positioning fixturing apparatus upon the external surface of the cell growth container. This assembly is inserted into a rotation container, which is rotated by a rotation apparatus.

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Troy, MI, United States of America

Michael J Borrelli