Table 1.

The comparison among different approaches to PCSK9 inhibition.

	MAbs	siRNA	ASO	Small molecules	Mimetic peptides	Adnectin	Vaccination
Structure	Monoclonal antibody	Double-stranded RNA	Single-stranded RNA	Protein	Peptide	Protein	Peptide
Administration	Once or Twice monthly, Subcutaneous injection	Twice yearly, Subcutaneous injection	Monthly, Subcutaneous injection	Daily, Oral administration	Injection administration	Subcutaneous or intravenous injection	Once yearly, Subcutaneous injection
Mechanism to action	Blocking the extracellular interaction of PCSK9 with LDLR	PCSK9 synthesis inhibition through RNA interference	PCSK9 synthesis inhibition through RNA interference	Blocking the intracellular or extracellular interaction between PCSK9 and enzyme or receptor	Blocking the extracellular inter action between PCSK9 and LDLR	Blocking the extracellular interaction of PCSK9 with LDLR	Eliciting production of autoantibodies against PCSK9
Efficacy	LDL-C 60%, PCSK9 60% reduction	LDL-C 50%, PCSK9 70% reduction	LDL-C 25–50%, PCSK9 50–85% reduction (Clinical + preclinical results)	LDL-C 50–60% reduction	LDLR 50% reduction (Preclinical results)	LDL-C 50%, PCSK9 > 90% reduction	LDL-C 50%, PCSK9 60% reduction (Only preclinical results)
Advantage	High specificity, No serious adverse reaction	High specificity, Infrequent dosing, Long-term effect, No serious adverse reaction	High specificity	Oral administration, Easy production, Low cost	High specificity, Easy production	High specificity, Easy production, Low cost	Long-term effect, Infrequent dosing, Easy production, Low cost
Disadvantage	Frequent subcutaneous dosing, Short shelf life, High cost	Subcutaneous dosing	Serious renal adverse event	Low selectivity, Non-tissue specific effect	Intravenous dosing	Frequent subcutaneous or intravenous dosing, Short half-life	Subcutaneous dosing
Current phase	Approved	Phase 3 on going	Phase 1 (terminated)	Phase 1	Preclinical	Phase 1	Phase 1 on gong
References	(51, 52)	(67)	(74, 75)	(90, 91)	(107–112)	(119, 120)	(122–124)

MAbs, monoclonal antibody; siRNA, small interfering RNA; ASO, antisense oligonucleotide; LDLR, LDL receptor.