Table 2.

Tgerapectic agents against hepatitis B virus currently in clinical development

Mode of actions	Target	Stage of development	Ref.
Entry inhibitions	NTCP	Myrcludex in phage 2	[14,123]
cccDNA
Formation inhibitions	DSS	Preclinical	[99]
Transcription inhibitions	ASO	IONIS-HBVRx in phase 1	[98]
Destabilization/degradation	ZFN	Preclinical	[100,101]
	TALEN	Preclinical	[102,103]
	CRISPR/Cas9	Preclinical	[109-117]
SiRNA	PgRNA	ARC-520 in phase 2	[95]
Nucleocapsid assembly inhibitions	Capsid formation	BAY4109 in phase 1	[93,95]
Nucleocapsid assembly inhibitions	Capsid formation	NV1221 in phase 1	[93,95]
Reverse transcription inhibitions	Polymerase	TAF in phase 3	[93,94]
Reverse transcription inhibitions	Polymerase	Cmx157 in phase 1/2	[93,95]
HBsAg release inhibitions	HBsAg secretion	Preclinical	[109]
HBsAg release inhibitions	HBsAg secretion	Rep2139 in phase 1/2	[110]
Immune modulating	TLR-7 agonist	GS-9620 in phase 2	[67,68]
	HBV-specific	Preclinical	[84]
	cIAPS	Preclinical	[86]

cccDNA: Covalently-closed circular DNA; ZFN: Zinc finger nuclease; TALEN: Transcription activator-like effector nuclease; CRISPR: Clustered regularly interspaced short palindromic repeat; Cas: CRISPR associated system; pgRNA: Pregenomic RNAs; HBsAg: Hepatitis B virus surface antigen; TLR: Toll-like receptor; HBV: Hepatitis B virus; cIAPS: Cellular inhibitor of apoptosis proteins; DSS: Disubstituted sulfonamide; ASO: Antisense oligonucleotides; TAF: Tenofovir Alafenamide; NTCP: Na⁺/taurocholate cotransporting polypeptide.