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RTB Lectin: a novel receptor- independent delivery system for lysosomal enzyme replacement therapies Enzyme replacement therapies have revolutionized patient treatment for multiple rare lysosomal storage diseases but show limited efectiveness for addressing pathologies in “hard-to-treat” organs and tissues including brain and bone. Here we investigate the plant lectin RTB as a novel carrier for human lysosomal enzymes. RTB enters mammalian cells by multiple mechanisms including both adsorptive-mediated and receptor-mediated endocytosis, and thus provides access to a broader array of organs and cells. Fusion proteins comprised of RTB and human α-L-iduronidase, the corrective enzyme for Mucopolysaccharidosis type I, were produced using a tobacco-based expression system. Fusion products retained both lectin selectivity and enzyme activity, were efciently endocytosed into human fbroblasts, and corrected the disease phenotype of mucopolysaccharidosis patient fbroblasts in vitro. RTB-mediated delivery was independent of high-mannose and mannose-6- phosphate receptors, which are exploited for delivery of currently approved lysosomal enzyme therapeutics. Thus, the RTB carrier may support distinct in vivo pharmacodynamics with potential to address hard-to-treat tissues. 发自小木虫Android客户端 |
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2楼2015-11-02 19:59:17