Table 3.

Gene delivery system for liver fibrosis^{76,80,91,93,96,}98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121.

Carrier	Gene	Target	Effect and mechanism of action	Ref.
Adenoviral vector + cytomegalovirus (Ad5-CMV)	Antisense-TGF-β1 mRNA	TGF-β synthesis in cultured HSCs	Abrogates TGF-β enhanced production of collagen and α-SMA	80
Adenoviral vector	Human urokinase plasminogen activator cDNA	Latent hepatic collagenases	Reduced α-Sma, increased Mmp-2, stimulated liver regeneration	98
Adenovirus + HBV vector (chimeric Ad-HBV shuttle vector)	Truncated MMP-8 gene (tMMP8)	HGF	Induced hepatocyte proliferation in liver cells without affecting other tissues	99
Adenoviral vector	HGF-encoding cDNA	Fibrogenic cytokines PDGF-bb and TGF-β1	Elevated HGF levels in the portal vein, decreased collagen level	100
Recombinant lentivirus particles	Artificial miRNAs	Pdgfrβ and Tgfbr2	Co-knockdowns the expressions of Tgfbr2 and Pdgfrβ, suppressed expressions of α-Sma, Col1a1, Mmps and Timp1	101
Recombinant adenoviral vector	β-Galactosidase	Hepatocytes	Decreased the expression of hepatocytes	102
Recombinant adenoviral vector	MMP-1	Hepatocytes	Decreased the number of activated HSCs, and increased hepatocyte proliferation	103
Recombinant adenoviral vector	MMP-8	Hepatocytes	Diminished hydroxyproline content, and up regulated expression of MMP-2 and MMP-3	104
Adeno-associated virus	ACE2	Hepatic ACE2 and angiotensin II	Reduction of angiotensin II, and inflammatory cytokine expression	105
Adeno-associated virus	Bone morphogenetic protein-7 (Bmp-7)	Tgfb	Long-term elevation of serum Bmp-7 concentrations and amelioration of CCl4-induced hepatic fibrosis	106
Adeno-associated virus	miR-221-3p	Hepatocytes	Faster resolution of the deposited ECM, and reduced secretion of C-C motif chemokine ligand 2
Hemagglutinating virus of Japan (HVJ)	Oncostatin M (OSM) cDNA	OSM protein in KCs	Reduced centrilobular necrosis and inflammatory cell infiltration, augmented hepatocyte proliferation, and suppressed hepatocytes apoptosis and fibrosis	107
Recombinant simian virus 40 vector (rSV40)	Recombinant insulin-like growth factor I (rIGF-I)	rIGF-I receptor	Reduced serum bilirubin, transaminases and liver fibrosis score, and increased expression of Hgf and Mmps	108
Minicircle vector (MC-hALR)	Regeneration/growth factor ERV1-like (ALR/GFER) gene	Tgfb, Pdgfb, α-Sma	Suppressed production of collagen I and α-Sma, Tgfb, Pdgfb, alleviated liver injury and fibrosis in rats	109
Plasmid	Artificial miRNA	CTGF, TGF-β1	Reduced hepatic fibrosis, and decreased levels of collagen I and α-SMA	110
Graphene-dendrimer nanostar	Plasmid encoding for the collagenase MMP-9	Macrophages	Promoted macrophage switch from inflammatory M1 to pro-regenerative M2 in three days	111
pCMV-Luc plasmid	Mmp-13 gene	Hepatocytes	Reduced liver fibrosis, and improved efficiency of hydrodynamic gene delivery	93
psiCHECK-2	miR-378a-3p, miR-378b, miR-378d	Gli3 in activated HSC	Accelerated expression of fibrotic genes and hedgehog signaling pathway	112
Lentivirus	miR-122	Type I collagen	Decreased collagen, Fn1 and Srf levels in the liver of CCl4-treated mice	113
Lentivirus	miRNA-101 family members	–	Attenuated profibrogenic Tgfb signalling and suppressed Tgfb-induced hepatocyte apoptosis and the inhibited cell proliferation	91
Lentivirus	Atp7b gene	Copper transport protein	Lowered liver copper levels, and decreased fibrotic tissue	114
Lentivirus	MiR-542-3p	BMP-7	Reduced liver fibrosis	115
pPB-modified stable nucleic acid LNPs	siRNA	Heat shock protein 47	Inhibitory effect on TAA-induced hepatic fibrosis with high gp46 mRNA expression	116
Poly (lactide-co-glycolide)-polyspermine-poly (ethylene glycol)-vitamin A (PLGA-PSPE-PEG-VA)	Co-delivery of silibinin and siCol1α1	Activated HSCs	Targeted activated HSCs specifically, decreased collagen I production and ameliorated liver fibrosis	117
CXCR4-targeted NPs	CXCR4+ sorafenib and MEK inhibitor	ERK in activated HSCs	Prevented activation of ERK in activated HSCs, anti-fibrotic effects in the CCl4-induced murine model	118
Ultrasound-targeted microbubbles	HGF	Collagen I and HGF	HGF delivery into the fibrotic liver and production of an anti-fibrosis effect	79
CSLNs	siCtgf	Pro-fibrotic genes in HSCs	Reduced collagen content Tnfa, Tgfb, IL-6, and Ctgf significantly, improved pathophysiological symptoms in rats	119
VA-polyethylene glycol polyethyleneimine-poly(N-(N′,N′-diisopropylaminoethyl)-co-benzylamino) aspartamide	miRNA-29b and miRNA-122	HSC	Improved liver function, and relieved hepatic fibrosis	120
Poly(amine-co-ester) NPs	Nogo-B siRNA	Liver	Suppressed Nogo-B protein in the liver up to 60% after systemic administration	121