News Release
CARLSBAD, Calif., Feb. 17 /PRNewswire/ -- The Immune Response Corporation (Nasdaq: IMNR - news) announced today that their scientists have synthesized a proprietary new human Factor VIII gene, which may lead to improvements in the development of gene therapy for people with hemophilia A. In animal studies, the Company has shown that the new Factor VIII gene can be expressed (turned on) at higher levels in the mouse liver when compared to the wild type (natural) human Factor VIII gene and that the new gene encodes a fully functional Factor VIII protein. These results were recently presented at the Keystone Symposia, ``Gene Therapy: The Next Millennium.'
Gene therapy is intended to treat certain genetic disorders by replacing the missing or defective gene(s) such as the blood coagulation-related Factor VIII gene, which is defective in people with the bleeding disorder known as hemophilia A. This gene defect leads to a deficiency in functional protein Factor VIII, which is essential for normal clotting of the blood. The World Federation of Hemophilia estimates that the incidence of hemophilia A in the world population is one in ten thousand males. Worldwide, approximately 350,000 people have severe or moderate hemophilia A and suffer from crippling and potentially life-threatening bleeding episodes. The Immune Response Corporation is developing non-viral gene therapies to treat disorders such as hemophilia A and B as well as infectious diseases such as hepatitis.
``An important aspect of gene therapy is to use a replacement gene that will be expressed at sufficient levels and duration to achieve a therapeutic benefit in the patient. We believe that this new Factor VIII gene may represent an improvement in current Factor VIII genes for hemophilia A. We have demonstrated the new Factor VIII gene is expressed at high levels in liver parenchymal cells (where the protein is naturally produced) and its product is secreted as fully functional Factor VIII protein,' said Charles R. Ill, Ph.D., Sr. Director of Molecular and Cellular Biology at The Immune Response Corporation. ``Using a technique called silent codon mutagenesis, we were able to synthesize a new coding sequence for the Factor VIII gene in which some 'undesirable' nucleotides were changed to desirable ones.' The mutations in the gene sequence that were introduced by the scientists do not interfere with the procoagulant activity of the Factor VIII protein product, Dr. Ill added.
In order to use a gene for gene therapy, the gene must be expressed. When a gene is turned on or 'expressed,' the cellular machinery copies the gene into another molecule called RNA (ribonucleic acid). RNA then undergoes modifications or processing before it is exported out of the nucleus and into the cytoplasm where protein production actually occurs. Cellular machinery in the cytoplasm translates the RNA code into amino acids, which are then assembled in a precise manner into a protein.
The Company's scientists have identified certain regions or sequences of the Factor VIII gene, which are involved in 'splicing' (an RNA modification process) and are thought to be detrimental to the stability and export of the RNA after its production in the cell. Taking advantage of the redundancy of the genetic code, the scientists were able to synthesize a new coding sequence for the Factor VIII gene, which eliminates these sites while preserving the original amino acid sequence of the protein.
The new Factor VIII gene is a culmination of research originally presented at the XXIII International Congress of the World Federation of Hemophilia held in The Hague, The Netherlands, May 1998, for which Dr. Ill and co-workers were awarded The Henri Horoszowski Memorial Prize for Outstanding Presentation. In collaboration with scientists at the Salk Institute, a component of this gene, responsible for its liver-specific expression properties, was reported in the March 1999 Proceedings of the National Academy of Science in an article entitled, ``Sustained correction of bleeding disorder in hemophilia B mice by gene therapy.'
The Immune Response Corporation is a biopharmaceutical company based in Carlsbad, California, developing immune-based therapies to induce specific T-cell responses for the treatment of HIV and autoimmune diseases. In addition, the Company is working on cancer vaccines and gene therapy. |
