BIOPRODUCTION OF A PLEIOTROPIC REGULATORY CYTOKINE FOR ORAL ADMINISTRATION AGAINST HUMAN AUTOIMMUNE DISEASES
A.B. Lucas S.S.
Interleukin-13 (IL-13) is a pleiotropic regulatory cytokine that plays a protective role against many autoimmune-associated diseases such as type-1 diabetes (T1D) and rheumatoid arthritis. To develop an IL-13-based immune therapy for treating such diseases with high efficiency, unique low cost, and suitability for oral administration, I generated transgenic plants last year to express recombinant human IL-13 (rhIL-13). The objective of this year’s study is to characterize the plant-derived transgenic protein at both molecular and functional levels. Northern blotting showed that the introduced rhIL-13 gene is correctly transcribed in transgenic plants. Protein immunoblotting analysis coupled with enzymatic deglycosylation demonstrated that the plant-derived rhIL-13 protein is expressed in the form of three major glycosylated peptides, similar to that found in its human counterpart. The expression levels of rhIL-13 in transgenic leaf tissues were found to reach as high as 0.15% of total soluble protein (TSP). In vitro bioassays using a factor-dependent human erythroleukemic cell line, TF-1, showed that the plant-derived rhIL-13 retains the biological functions of the authentic hIL-13 protein. Moreover, the plant-produced glycosylated rhIL-13 was found to be much less prone to pancreatic proteolysis, suggesting it is suitable for oral administration. Finally, results from the research lab’s feeding of nonobese diabetic (NOD) mice, an animal model for human T1D, with hIL-13 transgenic leaf tissues lowered the incidence of T1D. Taken together, these results suggest that transgenic plants may represent a novel cost-effective approach to the prevention and treatment of clinical human autoimmune diseases such as T1D through oral delivery of its expressed recombinant human cytokine IL-13.
|Second Award – Medicine and Health Sciences – Presented by Intel Foundation||$1500|
|Fifth Award $250 – American Society for Microbiology||$250|