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

Table 2 Summary of studies using small RNA and DNA based therapies in liver cirrhosis

Strategy	Target gene	Biological effects	Ref.
Antisense ODN	TGF-β1	Inhibition of liver fibrogenesis in vivo (bile duct ligation) and in vitro (activated HSCs)	[50]
	TβRI and TβRII	Exogenous antisense TβRI and TβRII block in pig serum induced liver fibrosis	[51]
	TIMP-1	Preventive effect on immune induced liver fibrosis progression	[54]
	TIMP-2 (seq1 and seq2)	Hydrodynamic injection of TIMP-2 antisense prevented the progression of liver fibrosis	[55]
siRNA	TGF-β1	TGF-β1 shRNA effectively inhibited CCl4-induced liver fibrosis	[62]
	TGF-β1	Inhibition of the expression of TGF-β1 and inflammatory cytokine in HSC-T6	[63]
	Collagen specific chaperon (gp46)	Effectively resolved the hepatic collagen deposition and prolonged survival in DMN-induced liver fibrosis	[64]
	PDGF receptor beta small subunit (GFAP promoter)	HSCs-specific PDGFR-beta shRNA attenuates CCl4-induced acute liver injury and bile duct ligation-induced chronic liver fibrosis	[65]
	Ubc 13	Galactosylated liposome/siRNA complex effectively exhibited the hepatocyte selective gene silencing	[79]
miRNA	miR-27a and 27b	Down regulation of miR-27a and 27b changed from activated HSC to quiescent HSC	[82]
	miR-29b	Negative regulator for the type I collagen and Sp1 in HSC	[83]
	miR-29 family	Modulation of TGF-β1 and NF-κB signaling pathway in CCl4-induced liver fibrosis	[84]
	miR-199a, miR-199a*, miR200a and miR-200b	Highly expressed miRNAs by miRNA microarray analysis in CCl4-induced liver fibrosis	[85]
Decoy ODN	NF-κB	Inhibition of inflammatory changes and fibrosis during CCl4-induced liver fibrosis	[96]
	Sp1	Inhibition of proliferation and fibrotic gene synthesis in activated HSCs	[99]
	Sp1	Inhibition of TGF-β1 and matrix gene expression in CCl4-induced liver fibrosis	[100]
	NF-κB and Sp1	Inhibition of fibrogenic and proinflammatory response in CCl4-induced liver fibrosis	[104]

ODN: Oligodeoxynucleotide; HSC: Hepatic stellate cell; TβR: TGF-β1 receptor; TIMP: Tissue inhibitor of metalloproteinase; DMN: Dimethylnitrosamine; GFAP: Glial fibrillary acidic protein; CCl₄: Carbon tetrachloride.