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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 \u03b1-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 <jats:italic>in vitro<\/jats:italic>. 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 <jats:italic>in vivo<\/jats:italic> pharmacodynamics with potential to address hard-to-treat tissues.<\/jats:p>","DOI":"10.1038\/srep14144","type":"journal-article","created":{"date-parts":[[2015,9,18]],"date-time":"2015-09-18T10:45:17Z","timestamp":1442573117000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["RTB Lectin: a novel receptor-independent delivery system for lysosomal enzyme replacement therapies"],"prefix":"10.1038","volume":"5","author":[{"given":"Walter","family":"Acosta","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge","family":"Ayala","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maureen C.","family":"Dolan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carole L.","family":"Cramer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2015,9,18]]},"reference":[{"key":"BFsrep14144_CR1","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1517\/14728214.13.1.197","volume":"13","author":"G Grabowski","year":"2008","unstructured":"Grabowski, G. 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