Linda M Robles, Laura H Reichenberg, James H Grissom Ⅲ, Richard J Chi, Kenneth J Piller
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引用次数: 0
Abstract
It is estimated that multiple sclerosis (MS) affects over 2.8 million people worldwide, with a prevalence that is expected to continue growing over time. Unfortunately, there is no cure for this autoimmune disease. For several decades, antigen-specific treatments have been used in animal models of experimental autoimmune encephalomyelitis (EAE) to demonstrate their potential for suppressing autoimmune responses. Successes with preventing and limiting ongoing MS disease have been documented using a wide variety of myelin proteins, peptides, autoantigen-conjugates, and mimics when administered by various routes. While those successes were not translatable in the clinic, we have learned a great deal about the roadblocks and hurdles that must be addressed if such therapies are to be useful. Reovirus sigma1 protein (pσ1) is an attachment protein that allows the virus to target M cells with high affinity. Previous studies showed that autoantigens tethered to pσ1 delivered potent tolerogenic signals and diminished autoimmunity following therapeutic intervention. In this proof-of-concept study, we expressed a model multi-epitope autoantigen (human myelin basic protein, MBP) fused to pσ1 in soybean seeds. The expression of chimeric MBP-pσ1 was stable over multiple generations and formed the necessary multimeric structures required for binding to target cells. When administered to SJL mice prophylactically as an oral therapeutic, soymilk formulations containing MBP-pσ1 delayed the onset of clinical EAE and significantly reduced developing disease. These results demonstrate the practicality of soybean as a host for producing and formulating immune-modulating therapies to treat autoimmune diseases.
期刊介绍:
Plant Biotechnology is an international, open-access, and online journal, published every three months by the Japanese Society for Plant Biotechnology. The journal, first published in 1984 as the predecessor journal, “Plant Tissue Culture Letters” and became its present form in 1997 when the society name was renamed to Japanese Society for Plant Cell and Molecular Biology, publishes findings in the areas from basic- to application research of plant biotechnology. The aim of Plant Biotechnology is to publish original and high-impact papers, in the most rapid turnaround time for reviewing, on the plant biotechnology including tissue culture, production of specialized metabolites, transgenic technology, and genome editing technology, and also on the related research fields including molecular biology, cell biology, genetics, plant breeding, plant physiology and biochemistry, metabolic engineering, synthetic biology, and bioinformatics.