Table 2 Current clinical trials involving RNA delivery

siRNA-EphA2-DOPC

siRNA

EphA2

Lipid nanoparticle

Intravenous infusion

Solid cancer

NCT01591356

I

TD101

siRNA

K6a

Naked (unmodified)

Intralesional injection

Pachyonychia congenita

NCT00716014

I

Atu027

siRNA

PKN3

Lipid nanoparticle

Intravenous infusion

Solid cancer

NCT00938574

I

ND-L02-s0201

siRNA

HSP47

Lipid nanoparticle

Intravenous infusion

Liver fibrosis

NCT01858935, NCT02227459

I

DCR-PH1

siRNA

Glycolate oxidase

Lipid nanoparticle

Intravenous infusion

Primary hyperoxaluria type 1

NCT02795325

I

STP705

siRNA

TGF-1β and Cox-2

Polymer nanoparticle

Intradermal injection

Hypertrophic scarring

NCT02956317

I/II

ALN-GO1

siRNA

Glycolate oxidase

Conjugate (GalNAc)

Subcutaneous injection

Primary hyperoxaluria type 1

NCT02706886

I/II

Fitusiran (ALN-AT3SC)

siRNA

Plasma antithrombin

Conjugate (GalNAc)

Subcutaneous injection

Severe hemophilia A or B

NCT02554773

I/II

ALN-CC5

siRNA

Complement component C5

Conjugate (GalNAc)

Subcutaneous injection

Paroxysmal nocturnal hemoglobinuria

NCT02352493

I/II

ALN-AS1

siRNA

ALAS-1

Conjugate (GalNAc)

Subcutaneous injection

Acute intermittent porphyria

NCT02949830

I/II

DCR-MYC

siRNA

MYC

Lipid nanoparticle

Intravenous infusion

Solid cancer

NCT02110563 NCT02314052

II/II

TKM 080301

siRNA

PLK1

Lipid nanoparticle

Liver injection Intravenous infusion Intravenous infusion

Liver cancer

Liver cancer Adrenocortical carcinoma

NCT01437007 NCT02191878 NCT01262235

I

I/II

I/II

siG12D-LODER

siRNA

KRASG12D

Degradable polymer

Local implantation

Pancreatic cancer

NCT01676259

II

Inclisiran (ALN-PCSSC)

siRNA

PCSK9

Conjugate (GalNAc)

Subcutaneous injection

Hypercholesterolemia

NCT03060577

II

PF-655

siRNA

RTP801

Naked (modified)

Intravitreal injection

Diabetic macular edema

NCT01445899

II

SYL1001

siRNA

TRPV1

Naked (modified)

Eye drops

Dry eye syndrome

NCT02455999

II

Bamosiran (SYL040012)

siRNA

β-2 adrenergic receptor

Naked (modified)

Eye drops

Glaucoma

NCT02250612

II

QPI-1007

siRNA

Caspase 2

Naked (modified)

Intravitreal injection

Acute nonarteritic anterior ischemic optic neuropathy

NCT02341560

II/III

QPI-1002

siRNA

p53

Naked (modified)

Intravenous infusion

Prevention of acute kidney injury

Delayed graft function in kidney transplant recipients

NCT02610283

NCT02610296

II

III

Patisiran (ALN-TTR02)

siRNA

TTR

Lipid nanoparticle

Intravenous infusion

Familial amyloid polyneuropathy

NCT01960348

III

ISTH0036

ASO

TGF-β2

Naked (modified)

Intravitreal injection

Glaucoma

NCT02406833

I

EZN-2968 (RO7070179)

ASO

HIF1A

Naked (modified)

Intravenous infusion

Liver cancer

NCT02564614

I

LErafAON-ETU

ASO

C-raf

Lipid nanoparticle

Intravenous infusion

Advanced cancer

NCT00100672

I

AKCEA-APOCIII-LRx

ASO

ApoCIII

Conjugate (GalNAc)

Subcutaneous injection

Elevated triglycerides

NCT02900027

I

BIIB067 (IONIS-SOD1Rx)

ASO

SOD1

Naked (modified)

Intrathecal injection

Amyotrophic lateral sclerosis

NCT02623699

I

AZD5312

ASO

Androgen receptor

Naked (modified)

Intravenous infusion

Prostate cancer

NCT02144051

I

Cenersen

ASO

p53

Naked (modified)

Intravenous infusion

Myelodysplastic syndrome

NCT02243124

I

IONIS-HTT Rx

ASO

Huntingtin

Naked (modified)

Intrathecal injection

Huntington's disease

NCT02519036

I/II

IONIS ANGPTL3-LRx

ASO

ANGPTL3

Conjugate (GalNAc)

Subcutaneous injection

Elevated triglycerides/familial hypercholesterolemia

NCT02709850

I/II

AZD9150

ASO

STAT3

Naked (modified)

Intravenous infusion

Solid cancer

NCT01563302

I/II

QR-010

ASO

CFTR (causes base insertion)

Naked (modified)

Nebulization (inhaled)

Cystic fibrosis

NCT02532764

I/II

SB012

ASO

GATA-3

Naked (modified)

Enema

Ulcerative colitis

NCT02129439

I/II

AEG35156

ASO

XIAP

Naked (modified)

Intravenous infusion

Solid cancer

NCT00882869

I/II

DS-5141b

ASO

Dystrophin (exon skipping)

Naked (modified)

Subcutaneous injection

Duchenne muscular dystrophy

NCT02667483

I/II

AKCEA-APO(a)-LRx

ASO

ApoA

Conjugate (GalNAc)

Subcutaneous injection

Hyperlipoproteinemia(a)

NCT03070782

II

Apatorsen (OGX-427)

ASO

Hsp27

Naked (modified)

Intravenous infusion

Solid cancer

NCT01829113

II

IONIS-HBV Rx

ASO

HBV surface antigen

Naked (modified)

Subcutaneous injection

Hepatitis B infection

NCT02981602

II

IONIS-GCGR Rx

ASO

GCGR

Naked (modified)

Subcutaneous injection

Type 2 diabetes

NCT02824003

II

ASM8

ASO

CCR3, β-chain of IL-3, IL-5, and GM-CSF

Naked (modified)

Nebulization (inhaled)

Allergen-induced asthma

NCT00822861

II

SB010

ASO

GATA-3

Naked (modified)

Nebulization (inhaled)

Asthma

NCT01743768

II

SB011

ASO

GATA-3

Naked (modified)

Topical

Atopic dermatitis

NCT02079688

II

G4460

ASO

C-myb

Naked (modified)

Intravenous infusion

Liquid cancer

NCT00780052

II

Prexigebersen (BP1001)

ASO

Grb2

Lipid nanoparticle

Intravenous infusion

Myeloid leukemia

NCT02781883

II

IONIS-FXI Rx

ASO

Factor XI

Naked (modified)

Subcutaneous injection

Clotting disorders

NCT02553889 NCT01713361

II

Aganirsen (GS-101)

ASO

IRS-1

Naked (modified)

Eye drops

Neovascular glaucoma

NCT02947867

II/III

Eteplirsen (AVI-4658)

ASO

Dystrophin (exon skipping)

Naked (modified)

Intramuscular injection

Duchenne muscular dystrophy

NCT02255552

III

Alicaforsen

ASO

ICAM-1

Naked (modified)

Enema

Pouchitis

NCT02525523

III

Volanesorsen

ASO

ApoCIII

Naked (modified)

Subcutaneous injection

Familial chylomicronemia syndrome

Familial partial lipodystrophy

NCT02658175

NCT02527343

III

II/III

IONIS-TTR Rx

ASO

TTR

Naked (modified)

Subcutaneous injection

Familial amyloid polyneuropathy

NCT01737398

III

Custirsen (OGX-011)

ASO

Clusterin

Naked (modified)

Intravenous infusion

Prostate cancer

Non small cell lung cancer

NCT01578655 NCT01630733

III

Lipo-MERIT

mRNA

Tumor-associated antigens

mRNA–Lipoplex

Intravenous infusion

Melanoma

NCT02410733

I

IVAC mutanome/warehouse

mRNA

Patient-specific tumor antigens

Naked mRNA

Intra-nodal

Triple negative breast cancer

Melanoma

NCT02316457

NCT02035956

I

TNBC-MERIT

mRNA

Tumor-associated antigens

mRNA–Lipoplex

Intravenous infusion

Triple negative breast cancer

NCT02316457

I

CV7201

mRNA

Rabies virus glycoprotein

Naked mRNA

Intramuscular injection

Rabies

NCT02241135

I

CV8102

mRNA

RNA-based adjuvant

Naked mRNA

Intramuscular injection

RSV, HIV, rabies

NCT02238756

I

mRNA-1851

mRNA

Hemagglutinin 7 (H7) protein

ND

Intramuscular injection

Influenza A

ND

I

mRNA-1440

mRNA

Hemagglutinin 10 (H10) protein

ND

Intramuscular injection

Influenza A

ND

I

mRNA MRK-1777

mRNA

Vaccine

ND

Intramuscular injection

Undisclosed

ND

I

mRNA AZD-8601

mRNA

VEGF-A

Naked (modified)

Intradermal

Cardiovascular disease

NCT02935712

I

mRNA-1325

mRNA

Viral antigenic proteins

Lipid nanoparticle

Intramuscular injection

Zika

NCT03014089

I/II

CV9103

mRNA

Tumor-associated antigens

Naked mRNA

ND

Prostate cancer

NCT00831467

I/II

mRNA

Tumor-specific antigens

Naked mRNA

Autologous dendritic cell therapy

Prostate cancer patients

NCT01197625

I/II

AGS-004

mRNA

Vaccine

Naked mRNA

Autologous dendritic cell therapy

HIV infections

NCT01069809, NCT02707900

I

II

mRNA

CT7, MAGE-A3, and WT1

Naked mRNA

Autologous dendritic cell therapy

Multiple myeloma

Acute myeloid leukemia

NCT01995708 NCT01686334

I

II

AGS-003-LNG

mRNA

Tumor-specific antigens

Naked mRNA

Autologous dendritic cell therapy

Non-small cell lung cancer

NCT02662634

II

iHIVARNA-01

mRNA

HIV target antigens

Naked mRNA

Intranodal route

HIV infections

NCT02888756

II

AGS-003

mRNA

Tumor-specific antigens

Naked mRNA

Autologous dendritic cell therapy

Renal cell carcinoma

NCT01482949 NCT00678119 NCT01582672

II

III