. 2021 Apr 6;13(4):e13243. doi: 10.15252/emmm.202013243

Table 3.

Clinically approved oligonucleotides.

Approval date		Drug name	Disease	Target	ASO sequence 5′–3′	Administration route/target tissues
FDA	EMA	Drug name	Disease	Target	ASO sequence 5′–3′	Administration route/target tissues
RNaseH
26 August 1998	29 July 1999	Fomivirsen (Vitravene)	Cytomegalovirus retinitis in immunocompromised patients	CMV major immediate‐early gene mRNA	dGs‐dCs‐dGs‐dTs‐dTs‐dTs‐dGs‐dCs‐dTs‐dCs‐dTs‐dTs‐dCs‐dTs‐dTs‐dCs‐dTs‐dTs‐dGs‐dCs‐dG	IVT / eye
29 January 2013	refused authorisation	Mipomersen (Kynamro)	Homozygous familial hypercholesterolemia	Apolipoprotein B‐100	Gs‐mCs‐mCs‐Ts‐mCs‐dAs‐dGs‐dTs‐dmCs‐dTs‐dGs‐dmCs‐dTs‐dTs‐dmCs‐Gs‐mCs‐As‐mCs‐mC	SC / liver
05 October 2018	05 July 2018	Inotersen (Tegsedi)	Hereditary transthyretin amyloidosis	Transthyretin	mTs‐mCs‐mTs‐mTs‐Gs‐dGs‐dTs‐dTs‐dAs‐dmCs‐dAs‐dTs‐dGs‐dAs‐dAs‐dAs‐mTs‐mCs‐mCs‐mC*‐3′	SC / liver
Under review	03 May 2019	Volanesorsen (Waylivra)	Familial chylomicronemia syndrome, hypertriglyceridemia and familial partial lipodystrophy	Apolipoprotein CIII	As‐Gs‐mCs‐Ts‐Ts‐dmCs‐dTs‐dTs‐dGs‐dTs‐dmCs‐dmCs‐dAs‐dGs‐dmCs‐Ts‐Ts‐Ts‐As‐T	SC / liver
Splice modulation
01 June 2019‡	N/A	Milasen	Neuronal ceroid lipofuscinosis 7, Batten's disease	MFSD8 exon 6	As‐As‐Ts‐Gs‐Ts‐Ts‐As‐Gs‐Ts‐Gs‐mCs‐Ts‐Ts‐Gs‐Ts‐Ts‐Gs‐As‐Gs‐Gs‐Gs‐mC	IT / CNS
19 September 2016	refused authorisation	Eteplirsen (Exondys51)	Duchenne muscular dystrophy	Dystrophin exon 51	CTCCAACATCAAGGAAGATGGCATTTCTAG	IV / skeletal muscle
12 December 2019	Under review	Golodirsen (Vyondys 53)	Duchenne muscular dystrophy	Dystrophin exon 53	GTTGCCTCCGGTTCTGAAGGTGTTC	IV / skeletal muscle
August 2020	Under review	Viltolarsen† (Viltepso)	Duchenne muscular dystrophy	Dystrophin exon 53	CCTCCGGTTCTGAAGGTGTTC	IV / skeletal muscle
23 December 2016	30 May 2017	Nusinersen (Spinraza)	Spinal muscular dystrophy	Survival motor neuron 2 exon 7	mTs‐mCs‐As‐mCs‐mTs‐mTs‐mTs‐mCs‐As‐mTs‐As‐As‐mTs‐Gs‐mCs‐mTs‐Gs‐G	IT / CNS
Aptamer
17 December 2004	31 January 2006	Pegaptanib (Macugen)	Age‐related macular degeneration	Vascular endothelial growth factor	40 kDa PEG‐5′‐C^F‐G^‐G^‐A‐A‐U^F‐C^F‐A^‐G^‐U^F‐G^‐A^‐A^‐U^F‐G^‐C^F‐U^F‐U^F‐A^‐U^F‐A^‐C^F‐A^‐U^F‐C^F‐C^F‐G^‐3′‐3′‐dT‐5′	IVT / eye
RNAi
10 August 2018	27 August 2018	Patisiran (Onpattro)	Hereditary transthyretin amyloidosis	Transthyretin	5′‐G‐U^‐A‐A‐C^‐C^‐A‐A‐G‐A‐G‐U^‐A‐U^‐U^‐C^‐C^‐A‐U^‐dT‐dT‐3′ 3′‐dT‐dT‐C‐A‐U^‐U‐G‐G‐U‐U‐C‐U‐C‐A‐U^‐A‐A‐G‐G‐U‐A‐5′ LNP formulated	IV / liver
20 November 2019	02 March 2020	Givosiran (Givlaari)	Acute hepatic porphyria	Aminolevulinate synthase 1	5′‐Cs^‐As^‐G^‐A^‐A^‐A^‐G^F‐A^‐G^F‐U^‐G^F‐U^‐C^F‐U^‐C^F‐A^‐U^‐C^‐U^‐U^‐A^‐3′ 3′‐Us^‐Gs^‐G^‐U^F‐C^‐U^F‐U^‐U^F‐C^‐U^F‐C^‐A^F‐C^‐A^F‐G^‐A^F‐G^‐U^F‐A^‐G^F‐As^F‐As^F‐U^‐5′ GalNAc Conjugate	SC / liver
	16 October 2020¥	Lumasiran (Oxlumo)	Primary hyperoxaluria type 1	Hydroxiacid oxidase 1	5′‐As^‐Cs^‐C^‐U^‐G^‐A^‐A^‐A^F‐G^‐U^F‐A^‐G^‐G^‐A^‐C^F‐C^F‐U^‐U^F‐U^‐A^‐Us^‐As^F‐U^‐3′ 3′‐Gs^‐As^‐Cs^‐U^‐U^‐U^‐C^F‐A^‐U^F‐C^F‐C^F‐U^‐G^‐G^‐A^‐A^‐A^‐U^‐A^‐U^‐A^‐5′ GalNAc Conjugate	SC / liver
	16 October 2020¥	Inclisiran	Atherosclerotic cardiovascular disease	Proprotein convertase subtilisin‐kexin type 9	5′‐As^‐C^Fs‐As^‐A^F‐A^F‐A^F‐G^‐C^F‐A^‐A^F‐A^‐A^‐C^‐A^F‐G^‐G^F‐U^‐C^F‐U^‐A^‐Gs^‐As^‐A^‐3′ 3′‐U^‐G^‐U^‐U^‐U^‐U^‐C^‐G^‐U^‐U^‐dT‐U^‐G^F‐U^‐C^F‐C^‐A^‐G^‐As^‐Us^‐C^‐5′ GalNAc Conjugate	SC / liver

s, phosphorothioate linkage; *, 2′‐MOE; d, 2′‐deoxy; m, 5‐methyl; ^F, 2′‐F; ^, 2′‐OMe; italicised, PMO; † Viltolarsen approval by Japanese Ministry of Health Labour and Welfare, 25 March 2020; ‡ Milasen approved by FDA for clinical testing only, ¥, lumasiran and inclisiran received positive opinion for marketing by the CHMP.