Treaments - RNA based Treatment tools for Prion Disease
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RNAi
Gene silencing using RNA interference has revolutionized biology. Since its discovery, RNA interference has rapidly become a powerful tool for disrupting gene function and as a result, not only has it accelerated gene characterization studies but has been seen as a potential therapy in the treatment of many diseases (1). The PrPC gene of Prion disease has long fascinated scientists from the beginning of the identification of Prion disease. From its involvement in the replication and therefore, the pathogenesis of Prion disease, it has been seen as an attractive therapeutic target (2). Since Prion disease is beginning to have a strong impact on the human society as seen from the increased number of cases of Creutzfeldt Jakob Disease (CJD), being able to suppress the PrPC gene expression in CJD patients is a future mission and RNA interference has been seen to hold much promise to this. While RNA interference by itself is unable to allow for the stable suppression of PrPC expression (3), other methods which incorporate RNA interference have to be examined. Combining lentiviruses with RNA interference has paved the way for successful suppression of the PrPC gene in humans in the future and has indicated that suppression of the Prion protein permanently is a possible event (4, 5). Loss of function techniques such as RNA interference will be helpful in gaining more insight into the physiological role of the Prion protein, PrPC. Based on results obtained, the best way to lead to the suppression of CJD PrPC in vivo is to expand on the studies already conducted. The human brain is much larger than that of mice, which were used as the model organism in many studies. It was confirmed that the mice with high concentration of lentiviral vectors in the brain cells survived longer (4). Since the human brain is larger in size, to deliver high concentration of lentivectors throughout the human brain, multiple catheters or/and pharmacological opening of the blood brain barrier may be applied to allow for the widespread transduction of the lentivectors (4). After perfecting the procedures of the insertion of RNAi by lentivectors and overcoming the barriers during these procedures in a large brain sized mammal, preferably cow (a natural host of Prion disease), it can be certain that the suppression of Prion protein permanently in human beings will be carried out in the near future.
References:
1. Kong Q. RNAi: a novel strategy for the treatment of Prion diseases. The Journal of Clinical Investigation 2006; 116: 3101-3103.
2. Tilly G, Chapuis J, Vilette D, Laude H, Vilotte JL. Efficient and specific down-regulation of Prion protein expression by RNAi. Biochemical & Biophysical Research Communication 2003; 305: 548-551.
3. Daude N, Marella M, Chabry J. Specific inhibition of pathological Prion protein accumulation by small interfering RNAs. Journal of Cell Science 2003; 116: 2775-2779.
4. Pfeifer A, Eigenbrod S, Al-Khadra S, Hofmann A, Mitteregger G, Moser M, Bertsch U, Kretzschmar H. Lentivector-mediated RNAi efficiently suppresses Prion protein and prolongs survival of scrapie-infected mice. The Journal of Clinical Investigation 2006; 116: 3204-3210.
5. Golding MC, Long CR, Carmell MA, Hannon GJ, Westhusin ME. Suppression of Prion protein in livestock by RNA interference. PNAS 2006; 103: 5285-5290.