Treaments - RNA based Treatment tools for Prion Disease

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RNA Aptamers

RNA aptamers offers the abilities to distinguish between the Prion proteins (1), and modified to become diagnostics and therapeutic tools. RNA aptamers hold an advantage over antibody technology by not being restricted by immunoprotected proteins (2), by having higher binding affinities, and by being easier to modify and produce chemically (3). Researchers have shown that RNA aptamers have the ability to inhibit PrPC to PrPSC conversion (1), as well as to reduce PrPSC formation (4). This illustrates the advantages associated with RNA aptamers compared to antibody technologies in investigating Prion diseases, and also illustrates the abilities of RNA aptamers to succeed as diagnostic and therapeutic options.

Figure 1. Model proposed by Proske et al. that attempts to explain how RNA aptamers reduce misfolded prion formation.(4).

References:

1. Rhie A, Kirby L, Sayer N, Wellesley R, Disterer P, Sylvester I, Gill A, Hope J, James W, Tahiri-Alaoui A. Characterization of 2'-flouro-RNA aptamers that bind preferentially to disease-associated conformations of prion protein and inhibit conversion. The Journal of Biological Chemistry 2003; 278:39697-39705.

2. Bunka DHJ, Stockley PG. Aptamers come of age – at last. Nature Reviews Microbiology 2006; 4:588-596.

3. Sekiya S, Noda K, Nishikawa F, Yokoyama T, Kumar PKR, Nishikawa S. Characterization and application of a novel RNA aptamer against the mouse prion protein. J. Biochem. 2006; 139:383-390.

4. Proske D, Gilch S, Wopfner F, Schatzl HM, Winnacker EL, Famulok M. Prion-protein-specific aptamer reduces PrPsc formation. ChemBioChem 2002; 3:717-725.