Grant: Strategic Projects - Group

This proposal aims to develop a powerful new expression system to produce and deliver inexpensive and high quantities of human therapeutic proteins for the treatment of Type 1 diabetes. The new expression system is based on the utilization of green algae by means of chloroplast transformation. The chloroplast is a membrane-bound organelle found in green algae and plant cells that conducts photosynthesis. There are many copies of chloroplast DNA per cell in both green algae and higher plants, and therefore chloroplast transformation has the potential to generate large amounts of foreign proteins due to the high copy number amplification of the transforming DNA.No effective therapy has been available for the treatment of type 1 diabetes in humans. Conventional insulin replacement can improve glycemic control, but is by no means a cure. While islet transplantation may be an effective treatment for diabetes, its use is limited by me short supply of human islets. Moreover, islet transplant patients still require life-long imiminosuppression to prevent rejection of the graft, which could lead to serious side effects. The induction of tolerance to a soluble protein by oral administration represents an attractive immune-based therapy for the treatment of autoimmune disease such as Type 1 diabetes, but requires the administration of high and repeated doses of antigen, which could be potentially very difficult and expensive to produce. The specific objectives of this project are to use Chlamydomonas chloroplast to produce the human islet protein glutamic acid decarboxylase (GAD) and insulin, as well as the immunoregulatory molecule interleukin-4 (IL-4) for therapy of Type 1 diabetes. The success of this project should lead to the development of unique, lower cost, immune-based therapies for Type I diabetes, with increased efficacy, and fewer side effects than previously existing treatment options.