RNA interference and antiviral therapy

Table 3 Strategies designed to inhibit HBV replication via RNA interference

Target gene	RNAi inducer (length)	Promoter	Vector	Model	Delivery methods	Inhib. of virus prod. (fold)	Reference
In vitro studies
C	siRNA (21 bp)	-	-	Huh-7, HepG2	Transfection	-4-5	[95]
	siRNA (19 bp)	-	-	HepAD38, HepAD79	Transfection	-50	[96]
C, X	shRNA (19 bp)	hH1	Plasmid	Huh-7, HepG2.2.15	Transfection	2-20	[97]
C, S, P, X, DR	shRNA (21-24 bp)	mU6	Plasmid	HepG2.2.15	Transfection	-2	[98]
	shRNA (21 bp)	hU6	Plasmid	HepG2	Transfection	> 30	[105]
S	shRNA (19 bp)	hH1	PFV, AAV	293T.HBs, HepG2.2.15	Transduction	4-9	[99]
In vivo studies
C, S, P, X	shRNA (25 bp)	hU6	Plasmid	Immunocompetent C57BL/6J mice, Immunocompromised NOD/SCID mice	Hydrodynamic transfection1	3-12	[100]
C, S	siRNA (21 bp)	-	-	Male NMRI mice	High-volume injection via tail vein1	-4	[101]
S	shRNA (19 bp)	hH1, hU6	Plasmid	BALB/c mice, HBsAg-transgenic FVB/N mice	Hydrodynamic transfection2	-9	[102]
P, S, X	shRNA (20 bp)	hH1	Plasmid	C57BL/6 HBV-transgenic mice	Hydrodynamic transfection1	19-99	[103]
P, S, X	shRNA (NR)	mU6	Adenovirus	HBV-transgenic mice	Hydrodynamic transfection	> 9	[104]

The fold inhibition of virus production refers to the results obtained with the most potent siRNA/shRNA. All siRNAs were prepared by chemical synthesis unless indicated otherwise. C: Core antigen; S: Surface antigen; P: Polymerase; X: X protein; DR: Direct repeat element; PFV: Prototype foamy virus; AAV: Adeno-associated virus; mU6: Mouse U6; hU6: Human U6; hH1: Human H1. 1shRNA expression plasmid/naked siRNA coinjected with the pHBV construct. 2shRNA expression plasmid simultaneously or subsequently injected with the pHBV/pSAg construct in BALB/c mice.