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AssigneeBaylor College of Medicine
InventorsBrendan Lee, Kilian Guse, Zhechao Ruan
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The invention relates to an adenoviral-based biological delivery and expression system for use in the treatment or prevention of osteoathritis in human or mammalian joints by long-term inducible gene expression of human or mammalian interleukin-1 receptor antagonist (Il-1Ra) in synovial cells, comprising a helper-dependent adenoviral vector containing a nucleic acid sequence encoding for human or mammalian interleukin-1 receptor antagonist (Il-1Ra), left and right inverted terminal repeats (L ITR and R ITR), the adenoviral packaging signal and non-viral, non-coding stuffer nucleic acid sequences, wherein the expression of the human or mammalian interleukin-1 receptor antagonist (Il-1Ra) gene within synovial cells is regulated by an inflammation-inducible promoter.
An adenoviral-based biological delivery and expression system, comprising a helper-dependent adenoviral vector containing a nucleic acid sequence encoding for human or mammalian interleukin-1 receptor antagonist (Il-1Ra), left and right inverted terminal repeats (L ITR and R ITR), an adenoviral packaging signal and non-viral, non-coding stuffer nucleic acid sequences, wherein the expression of the human or mammalian interleukin-1 receptor antagonist (Il-1Ra) gene is regulated by an inflammation-inducible promoter, which is located upstream of the reading frame of the nucleic acid sequence encoding for human or mammalian interleukin-1 receptor antagonist (Il-1Ra) and which is specifically activated by increased levels of immune stimulatory substances.
A pharmaceutical composition, comprising a helper-dependent adenoviral vector containing a nucleic acid sequence encoding for human or mammalian interleukin-1 receptor antagonist (Il-1Ra), left and right inverted terminal repeats (L ITR and R ITR), an adenoviral packaging signal and non-viral, non-coding stuffer nucleic acid sequences, wherein the expression of the human or mammalian interleukin-1 receptor antagonist (Il-1Ra) gene is regulated by an inflammation-inducible promoter, which is located upstream of the reading frame of the nucleic acid sequence encoding for human or mammalian interleukin-1 receptor antagonist (Il-1Ra) and which is specifically activated by increased levels of immune stimulatory substances.
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