RNAi silencing

Schijlen EGWM, Ric de Vos CH, Martens S, Jonker HH, Rosin FM, Molthoff JW, Tikunov YM, Angenent GC, van Tunen AJ, Bovy AG. 2007. RNAi silencing of chalcone synthase, the first step in the flavonoid biosynthesis pathway, leads to parthenocarpic tomato fruits. Plant Physiol 144 1520-1530. 

Further evidence that oenocytes are the cell type involved in hydrocarbon production was obtained by Wicker-Thomas et al. (unpublished data). The enzyme involved in the final step in hydrocarbon production, a cytochrome P450 that oxidatively decarbonylates aldehydes, was RNAi silenced specifically in oenocytes of both male and female D. melanogaster, resulting in marked inhibition of hydrocarbon production. The RNAi-silenced insects produced less than 10% of the hydrocarbon compared to control insects. Thus, the available evidence overwhelmingly supports oenocytes, whether associated with epidermal tissue or present in the peripheral fat body, as the site of cuticular hydrocarbon production. In some cases, even the shorter-chain hydrocarbon pheromones and pheromone precursors (see below) are produced in oenocytes. 

Figure 8.3 The sum of daidzin and glycitin as a percent of the total amount of isoflavones in plants containing a chalcone reductase RNAi silencing construct.

Figure 8.5 The total sapogenol per gram of soy obtained in control plants (Jack, 92B91, or unrelated transgcnics) and in soybean plants containing a p-amyrin RNAi silencing construct AC 16.

Bonetta L (2004) RNAi silencing never sounded better. Nat Methods 1 79-86... 

In sum, RNAi clearly has the potential to change the nucleic-based therapies for cancer, infectious diseases, and many other diseases. However, the universality of this approach, the types of genes that can be silenced using these strategies in human cells, remain unknown to date. 

Aigner A (2006) Gene silencing through RNA interference (RNAi) in vivo strategies based on the direct application of siRNAs. J Biotechnol 124 12-25... 

RNAi and ribozymes represent two additional approaches to gene silencing/down-regulation with therapeutic potential. RNAi is an innate cellular process that achieves silencing of selected genes via an anti-sense mechanism. It shares many characteristics with the antisense-based approach described above, but also some important differences, e.g. in the exact mechanism by which the antisense effect is achieved. 

RNAi Approach This is the use of short interfering RNA (siRNA, sometimes called small interfering or silencing RNA) to interfere with the expression of a particular gene. The siRNAs are double-stranded RNAs of 20-25 nucleotides. It is envisaged that if the biological pathway of a disease is identified, siRNA could interfere to turn off the activity of the gene involved in the pathway and provide therapeutic effect. 

RNAi has had an important impact on the development of novel disease models in animals, and it is likely that siRNAs, the trigger molecules for RNA silencing, will become an invaluable tool for the treatment of genetic disorders. The rational design of siRNAs, the introduction of chemical modifications into siRNAs to improve their pharmacokinetic and pharmacodynamic properties for in vivo application with high specificity, and the development of efficient delivery system will foster the therapeutic application of RNAi in AD and other neurodegenerative disorders (413,417). 

RNAi activity is most often induced using relatively small (generally 21-23 nucleotides long) segments of RNA that interfere with the activity (silence) of an endogenous... 

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