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Nucleic acids, including plasmid DNA (pDNA) and small interfering RNA (siRNA), are potential therapeutic macromolecules that have been widely explored for the treatment or prevention of various human diseases in the last three decades. pDNA encoding a therapeutic gene sequence can be introduced into the nuclei of the target cells to express functional proteins through transcription and translation in order to produce therapeutic effects. The therapeutic scope of pDNA includes a vast number of diseases, such as cancers (El-Aneed 2004; Yamamoto and Curiel 2005; Johnson, Morgan et al. 2009), genetic disorders (Gaspar, Parsley et al. 2004; Aiuti, Cattaneo et al. 2009; Griesenbach and Alton 2009), infections (Yu, Poeschla et al. 1994; Hashiba, Suzuki et al. 2001; Cull, Bartlett et al. 2002) and cardiovascular diseases (Stewart, Hilton et al. 2006; Vinge, Raake et al. 2008; Henry and Satran 2012). To date, over 1600 gene therapy clinical trials have been initiated (http://www. abedia. com/wiley/phases. php; Edelstein, Abedi et al. 2007). Apart from pDNA, siRNA has recently been intensively studied as a new therapeutic agent. RNA interference (RNAi) was discovered by Fire and colleagues based on the study of C. elegans (Fire, Xu et al. 1998). According to their observation, double-stranded RNA (dsRNA) mediates potent and specific silencing of homologous genes. Elbashir et al. demonstrated that the sequencespecific mediator of RNAi is 21-23-nucleotide siRNA produced from the cleavage of longer dsRNA by ribonuclease III (Elbashir, Lendeckel et al. 2001). Since then the mechanism of RNAi has been revealed and reviewed in many …