Small RNA- and DNA-based gene therapy for the treatment of liver cirrhosis, where we are?

Table 1 Advantages and disadvantages of small RNA and DNA based gene therapy

Strategy	Mechanisms of action	Advantages	Disadvantages
Antisense ODN	RNA-antisense ODN heteroduplex activates RNase H that can degrade the duplexesAntisense ODN physically block the ribosome translocation sterically by hybridization	Antisense ODN can be introduced directly into cellAvailability of chemical modification of antisense ODN	Stability in cells (endonucleolytic and exonucleolytic degradation)Modified antisense ODN stimulates the immune systemDesign and synthesis is more complicated compared with other strategies
siRNA	siRNA incorporated into RISC, which leads to the rapid degradation of the entire mRNA molecule	Great specificity and efficacy: thermodynamic end stability, target mRNA accessibility	Non-specific gene silencing
			Activation of immune response
			RNA degradation by endonuclease
			Expensive for larger experiments
miRNA	Small, non-protein coding RNAs that guide the post-transcriptional repression of mRNA binding at 3’ UTR region	miRNA ability to regulate multiple genesCost effective for long-term experiments	Need for cloning and verification of insert
			Activation of immune response
			RNA degradation by endonuclease
Decoy ODN	Double stranded oligonucleotide containing an enhancer cis-element	Specifically inhibits transcription factor function	Transfection efficiency and delivery to cells
	Target transcription factor binds to decoy ODN and block the interaction of target gene transcription	Allows for the regulation of endogenous and pathological gene expression	DNA degradation by endonuclease

RISC: RNA-induced silencing complex; siRNA: Small interfering RNA; miRNA: Micro RNA; RNase H: Ribonuclease H; 3’UTR: 3’-untranslated region; ODN: Oligodeoxynucleotides.