Figure 1. Transferrin receptor-mediated endocytosis of Fe3+.
The transferrin receptor (TfR) is a membrane bound protein that facilitates the transport of iron into cells (Ray 2010). The binding of transferrin-Fe+3 to TfR signals for endocytosis of the entire molecule . The molecule is transported to the endosomal compartment, iron is released and the rest of the molecule is incorporated back into the membrane. An aptamer will be selected against the transferrin receptor and modified post-selection with the addition of a functional lysosomal enzyme. This will enable the delivery of functional enzymes to lysosomes through aptamer-mediated endocytosis.
Though this form of enzyme replacement therapy is relatively new, there have been successful results, indicating that this therapeutic application of aptamers may be key to the future of lysosomal enzyme delivery. Researchers at UCLA have demonstrated the delivery of enzymes to cells deficient in lysosomal enzymes using the aptamer-mediated endocytosis method (Neufeld 2007). Chen et al. selected an aptamer against TfR and modified the aptamer with the attachment of α-l-iduronidase, a lysosomal enzyme. This aptamer complex was taken up by α-l-iduronidase-deficient mouse fibroblasts. The selection of an aptamer against TfR for aptamer-mediated endocytosis could have a revolutionary impact on the delivery of enzymes and treatment of various lysosomal storage disorders.
Human TfR from ARP- $259/ 50ug- http://www.biocompare.com/ProductDetails/1537096/Human-Transferrin-Receptor.html?
Chen, Chi-hong B. et. al. "Aptamer-based Endocytosis of a Lysosomal Enzyme." PNAS 105.41 (2008): 15908-5913.
Fong, Chin-To. "Lysosomal Storage Disorders." Merck & Co., Inc. Feb. 2010. Web. 04 Sept. 2010.
Futerman, Anthony H., and Gerrit Van Meer. "The Cell Biology of Lysosomal Storage Disorders." Nature 5 (2004): 554-65.
Neufeld, Elizabeth F. "Aptamer Mediated Correction of Lysosomal Enzyme Deficiency." The Regents of the University of California. UCLA,
Ray, Partha, and Rebekah R. White. "Aptamers for Targeted Drug Delivery." Pharmaceuticals 3 (2010): 1761-778.
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