Nucleic Acid Aptamer Selection against TfR for the Therapeutic Treatment of Lysosomal Storage Diseases

Lysosomal Storage Diseases are inherited metabolic disorders that result from dysfunctional lysosomal enzymes. These enzymes facilitate the digestion of macromolecules within eukaryotic cells (Fong 2010). The absence of functional lysosomal enzymes results in the accumulation of macromolecules within the cell and can lead to many harmful effects on cells, tissues and organs (Futerman 2004). An efficient method of enzyme delivery could alleviate many of the problems associated with these diseases. The selection of an aptamer against a target membrane bound protein involved in endocytosis could provide efficient system of enzyme delivery to lysosomes. Post-selection modification of the aptamer would be necessary to link an enzyme to the aptamer. This method of aptamer-mediated endocytosis and post-selection modification could have a significant impact on the future of targeted enzyme delivery, as the design is very versatile.

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 [1]. 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-


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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Gwen Stovall said...

Good start.

Try to avoid vague statements, like "can lead to many harmful effects on cells..." Instead, tell us specifically about the harmful effects.

Consider mentioning the number of people afflicted with such diseases or further describing the symptoms.

How will your selection differ from Chen's selection?

Alec Rezigh said...

Hey Bonnie, great start to the paper. I was just curious if there are benefits of functionalizing the aptamer after selection, instead of doing it before. Would it not be easier to select an aptamer from a pool already synthesized with the lysosomal enzyme? Does functionalizing afterward affect the conformation of TfR?

Brad Hall said...


Since Chen has already selected an aptamer for this purpose, you should describe his findings in more detail (1-2 sentences). How will yours be different (as Gwen suggested)? Are there other receptors that would work equally as well? It is certainly a good project and you have past experiments to backup the utility of these ideas, but you may consider how your aptamer would differ against TfR or if there are other receptors you could go after.

Nia_Fernandez said...

Make sure you keep your citations, font and general format constant throughout your reports.

Although you want to narrow down your information you don't want it to be too general when discussing the importance of your target especially when it is related to a particular pathway of an illness.