Table 2.

RNA-based drugs with either FDA approval or in late phase 3 clinical trials.

RNA class	Drug	Alternative name	Sponsor	Indication	Target gene	Target organ	Chemical modifications or delivery method	Administration route	Updated states	Comments	References
ASO	Fomivirsen	Vitravene, ISIS 2922	Ionis Pharmaceuticals	Cytomegalovirus Retinitis, HIV Infections	Immediate early region 2 (IE2) mRNA	Eye	2′-H	Intravitreal	Completed NCT00002187, NCT00002355	The first FDA-approved ASO medication (1998), withdrawal in Europe and USA in 2002	[118, 119]
	Mipomersen	Kynamro™, ISIS 301012	Kastle and IonisTherapeutics	Hypercholesterolemia, Atherosclerosis, Coronary Artery Disease	Apolipoprotein B (ApoB) mRNA	Liver	2′-MOE	Subcutaneous	Completed NCT01598948 NCT00607373 NCT01475825 NCT00770146 NCT00694109 NCT00794664 NCT00706849	The second-generation of ASOs (“Gapmers” ASO)	[120]
	Inotersen	ISIS 420915, Tegsedi, AKCEA-TTR-LRx	Ionis Pharmaceuticals	Hereditary ATTR Amyloidosis (hATTR)	Hepatic transthyretin (TTR) mRNA	Liver	2′-MOE	Subcutaneous	Completed NCT01737398
	Nusinersen	ISIS 396443, Sprinraza, IONIS-SMN Rx, BIIB058	Ionis Pharmaceuticals and Biogen	Spinal Muscular Atrophy (SMA)	Survival of motor neuron 2(SMN2) pre-mRNA splicing (exon 7 inclusion)	Central nervous system	2′-MOE, Fully modified	Intrathecal	Completed NCT02292537	Approved in 2016	[18, 121]
	Eteplirsen	AVI-4658, EXONDYS 51®	Sarepta Therapeutics	Duchenne Muscular Dystrophy (DMD)	DMD pre-mRNA splicing (exon 51 skipping)	Muscule	2′-MOE, PMO	Intravenous	Completed NCT02255552	The third-generation of ASO medications with advanced chemical modifications	[17, 121]
	Golodirsen	SRP-4053,Vyondys 53™	Sarepta Therapeutics	Duchenne Muscular Dystrophy (DMD)	DMD pre-mRNA splicing (exon 53 skipping)	Muscle	2′-MOE, PMO	Intravenous	Recruiting NCT02500381		[122]
	Viltolarsen	Viltepso, NS-065, NCNP-01	NS Pharma	Duchenne Muscular Dystrophy (DMD)	DMD pre-mRNA splicing (exon 53 skipping)	Muscle	2′-MOE, PMO	Intravenous	Recruiting NCT04768062 NCT04687020 NCT04060199		[123]
	Casimersen	SRP-4045, Amondys 45™	Sarepta Therapeutics, Inc.	Duchenne Muscular Dystrophy (DMD)	DMD pre-mRNA splicing (exon 45 skipping)	Muscle	PMO	Intravenous	Recruiting NCT03532542 NCT02500381		[124]
RNAi	Patisiran	ALN-TTR02, ONPATTRO™	Alnylam Pharmaceuticals	hATTR	TTR mRNA	Liver	PS, 2′-O-Me, 2′-F (LNP)	Intravenous	NCT03862807, NCT01960348	The first siRNA drug approved by FDA (2018)	[129]
	Givosiran	ALN-AS1, GIVLAARI	Alnylam Pharmaceuticals	Acute Hepatic Porphyria	Aminolevulinate synthase 1(ALAS1) mRNA	Liver	PS, 2′-O-Me, 2′-F GalNAc	Subcutaneous	NCT03338816	The second siRNA drug approved by FDA (2019)	[134]
	Lumasiran	ALN-GO1, OXLUMO	Alnylam Pharmaceuticals	Primary Hyperoxaluria Type 1 (PH1)	Hydroxyacid oxidase 1 (HAO1) mRNA	Liver	PS, 2′-O-Me, 2′-F GalNAc	Subcutaneous	Phae III active; NCT03905694 NCT03681184 NCT04152200	The third siRNA drug approved by FDA (2020)	[135]
	Inclisiran	ALN-PCSSC, LEQVIO	Alnylam and Novartis Pharmaceuticals	Hypercholesterolemia, Atherosclerotic Cardiovascular disease, Renal impairment	Proprotein convertase subtilisin kexin type 9 (PCSK9) mRNA	Liver	PS, 2′-O-Me, 2′-F GalNAc	Subcutaneous	Phase III completed; NCT03399370 NCT03400800 NCT03397121	Expand siRNA’s clinical portfolio beyond just orphan diseases.Provide sustained reductions in low-density lipoprotein (LDL) cholesterol levels with infrequent dosing (every 6 months).
	Vutrisiran	ALN-TTRSC02	Alnylam Pharmaceuticals	hATTR	TTR mRNA	Liver	PS, 2′-O-Me, 2′-F GalNAc	Subcutaneous	Phae III active; NCT04153149 NCT03759379	May prove to be a more clinically utilize, effective treatment option for hATTR than patisira
	Fitusiran	ALN-AT3SC	Alnylam Pharmaceuticals and Sanofi Genzyme	Hemophilia A / B	Antithrombin mRNA	Blood	PS, 2′-O-Me, 2′-F GalNAc	Subcutaneous	Phase III completed; NCT03974113 NCT03417102
	Nedosiran	DCR-PHXC	Dicerna Pharmaceuticals	Primary Hyperoxaluria	Hepatic lactate dehydrogenase mRNA	Liver	GalNAc	Subcutaneous	Phase III enrolling by invitation; NCT04042402	Compare with Lumasiran,it will have a potentially wider scope, since it is not limited to just PH1 patients.
	Teprasiran	QPI-1002	Quark Pharmaceuticals	Cardiac surgery	p53 mRNA	Kidney	2′-O-Me	Intravenous	Phase III completed; NCT02610296	The first systemically administered siRNA drug to enter human clinical trials
	QPI-1007		Quark Pharmaceuticals	Primary angle-closure glaucoma	Caspase 2 mRNA	Eye	2′-O-Me	Intravitreal	Phase II/III terminated: NCT02341560
	Tivanisiran	SYL-1001	Sylentis, S.A.	Dry eye disease	Transient receptor potential cation channel subfamily V member 1 (TRPV1) mRNA	Eye	Unmodified	Topical eye drop	Phase III completed; NCT03108664
Aptamer	Pegaptanib	Macugen®	Pfizer	Diabetic Macular Edema	VEGF (165 isoform)	Eye	Pegylated, all PO, 2′-F, and 2′-OMe; G and A methylated	Intravitreal injection	Phase IV Completed; NCT01486238 NCT01486238 NCT00406107 NCT00324116		[146]
mRNA vaccine	BNT162b2	Comirnaty®	BioNTech and Pfizer	Coronavirus disease 2019 (COVID-19)	Encodes the SARS-CoV-2 spike protein	Immune system	Nucleoside-modifed, lipid nanoparticle-formulated	Interventional	Completed NCT04816669 NCT04887948 NCT04713553 NCT05030974	The first two FDA-approved SARS-CoV-2 vaccines with >94% effectiveness in phase III clinical trial	[147]
	mRNA-1273		Moderna Therapeutics	COVID-19	Encodes the SARS-CoV-2 spike protein	Immune system	Lipid nanoparticle-formulated	Interventional	Completed NCT05030974		[148]