**8. References**

418 Myocarditis

intravenous injection of mice demonstrated significant reduction of virus titers and improvement of heart function compared to the control. This study showed for the first time that intravenously injected AAV2.9 has the potential to target RNAi to the heart and suggests AVV2.9-shRNA vectors as a novel therapeutic approach for cardiac disorders

<sup>A</sup> a'

b' B

ligand

NA-based gene silencing techniques have been successfully used in drug development. The major progress on ASON research is the chemical modifications and ligand conjugation to enhance drug stability and efficacy of delivery. The emergence of RNAi-mediated gene silencing techniques further provided new hope for this regard. Basically, siRNA silencing techniques can be used against any viral infection. Two major obstacles must, however, be overcome before it can become a broadly applicable standard therapy: the question of their specificity and efficient delivery to target cells. As siRNA can potentially cause off-site targeting and activate the immune system, minimizing the undesired effects must be considered in the drug design. Immense efforts have been undertaken to develop carrier

Fig. 3. Structural schematic of packaging RNA (pRNA) multimers as a drug targeted delivery vehicle. (A) pRNA dimer forms through the base-paring between the loops of an A'b-pRNA-siRNA and a B'a-pRNA-ligand. The shaded areas on the loops indicate the basepair interactions between the monomers. siRNA is released when intracellular Dicer cleaves the dsRNA, which is indicated by an arrow. (B) pRNA trimers can be stoichiometrically formed by hand-in-hand loop interactions, which contains 1:1:1 of their linked conjugates. (C) hexamers allow for a customizable, combined therapy where multiple drugs may be

siRNA or miRNA

Targeting ligand

(Fechner et al., 2008).

**A**

added to the same complex.

**6. Concluding remarks** 

siRNA

**<sup>B</sup> <sup>C</sup>**

Dicer


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