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Sci Rep. 2015 Sep 18;5:14144. doi: 10.1038/srep14144.

RTB Lectin: a novel receptor-independent delivery system for lysosomal enzyme replacement therapies.

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Arkansas Biosciences Institute at Arkansas State University-Jonesboro, State University, Arkansas, USA.
BioStrategies LC, State University, Arkansas, USA.
Department of Biological Sciences, Arkansas State University-Jonesboro, State University, Arkansas, USA.


Enzyme replacement therapies have revolutionized patient treatment for multiple rare lysosomal storage diseases but show limited effectiveness 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 efficiently endocytosed into human fibroblasts, and corrected the disease phenotype of mucopolysaccharidosis patient fibroblasts 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.

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