RA is a chronic inflammatory disease associated with joint destruction. In recent years understanding of disease process has led to the development of biologic disease modifying agents. Gene therapy can provide stable, regulated production of such therapeutic proteins.
Applying gene therapy vectors directly to the joint, the main site of inflammation, allows local delivery of proteins, thereby minimizing side-effects observed with systemic treatment. This, so called intra-articular delivery of therapeutic vectors is restricted to this enclosed compartment. Cells of the synovium, the synoviocytes, are easily reached via the joint cavity, are relatively long-lived, and thus represent an ideal target for gene therapy strategies.
The success of gene therapy for RA depends on achieving efficient, prolonged, safe, and regulated therapeutic gene expression in vivo. Gene transfer vectors can be categorized into two groups viral and non-viral vectors. A number of preclinical studies have shown the adeno-associated virus (AAV) to be an efficient vehicle for gene therapy for chronic diseases like RA. Clinical studies in a variety of diseases successfully demonstrated its potential for in vivo therapeutic gene transfer.
In gene therapy studies a "correct copy" or "wild type" gene is provided to the target cell that is missing this gene or has an inactive gene. Generally, it is not an exact replacement of the "abnormal," disease-causing gene, but rather extra, correct copies of genes are provided to complement the loss of function. In the treatment of rheumatic diseases the purpose of the gene therapy is different, since no specific defect in the gene is known to cause the disease.
In the area of autoimmune disease the focus is more directed towards modulation of the inflammatory process either with or without decreasing bone and cartilage destruction. Since the DNA by itself does not have the machinery to enter the cell, a vector, either viral or non-viral, needs to be used in order to facilitate cell entry of the therapeutic gene. Thereafter, the vector unloads its genetic material containing the therapeutic gene into the target cell and the cell can start to produce the therapeutic protein using its own machinery. Currently, the most efficient type of vectors are viruses that have been genetically modified to carry therapeutic genes. The viruses are natural occuring virusses of which most of the viral genes are removed to prevent replication of the virus and to reduce its immunogenicity. Arthrogen’s viral gene delivery platform is based on adeno-associated virusses.