TABLE 1.

TTR gene silencing agents

Nucleic acid target	Gene silencer a	Drug name	Formulation	Ligand conjugate	Admin route	Dose	Indication(s)	Phase b
RNA	ASO	Inotersen	–	–	SC	284 mg QW	ATTRv‐PN	Approved
		Eplontersen c	–	GalNAc	SC	45 mg Q4W	ATTRv‐PN ATTR‐CM	Phase 3
	siRNA	Patisiran	LNP	–	IV Infusion	0.3 mg/kg Q3W d	ATTRv‐PN	Approved
		Revusiran	–	GalNAc	SC	500 mg QW	ATTR‐CM	D/C
		Vutrisiran e	–	GalNAc	SC	25 mg Q3M	ATTRv‐PN ATTR‐CM	Approved Phase 3
DNA	CRISPR‐Cas9	NTLA‐2001	LNP	‐	IV Infusion	Up to 1 mg/kg single, one‐time dose f	ATTRv‐PN ATTR‐CM	Phase 1

Abbreviations: ASO, antisense oligonucleotide; ATTR(v), (hereditary) transthyretin amyloidosis; CM, cardiomyopathy; CRISPR, gene editing technology (targeted gene knockout); D/C, discontinued; GalNAc, triantennary N‐acetylgalactosamine; IV, intravenous; LNP, lipid nanoparticle; PN, polyneuropathy; SC, subcutaneous; siRNA, small interfering RNA (ribonucleic acid); Q3M, every 3 months; Q3W, every 3 weeks; Q4W, every 4 weeks; QW, every week.

^a ASO leads to RNase‐H1‐mediated mRNA degradation, siRNA leads to Ago2‐mediated mRNA degradation, and CRISPR‐Cas9 leads to DNA gene editing.

^b As of May 2022.

^c Eplontersen also known as ION‐682884, IONIS‐TTR‐LRx, and AKCEA‐TTR‐LRx.

^d Dosage for patients <100 kg; dosage is 30 mg for those ≥100 kg;

^e Vutrisiran also known as ALN‐TTRsc02.

^f Ascending dose trial underway.