Cover Story: It is an RNA world

Table 2. Accessible human tissues. Tissues that are accessible to single-stranded antisense and double-stranded RNAi therapeutics in human patients with exemplary therapeutics and targets, including notes on drug formulation. The table only includes tissues in which target engagement is supported by biomarker-based or clinical outcome-based evidence from in vivo human studies.


Antisense drug

RNAi drug

Delivery notes


Kynamro mipomersen, an antisense drug targeting apolipoprotein B-100 (APOB-100) mRNA, marketed by Isis Pharmaceuticals Inc. (NASDAQ:ISIS) and Genzyme Corp. unit of Sanofi (Euronext:SAN; NYSE:SNY)

Patisiran, an siRNA drug targeting transthyretin (TTR) mRNA, in Phase III testing by Alnylam Pharmaceuticals Inc. (NASDAQ:ALNY) and Genzyme

Patisiran is formulated as a lipid nanoparticle



ALN-TTRsc, an siRNA drug targeting TTR mRNA, in Phase II testing by Alnylam and Genzyme

ALN-TTRsc is formulated as an N-acetylgalactosamine (GalNAc) conjugate

Central nervous

system (CNS)

Isis-SMNRx, an antisense drug promoting splicing of survival of motor neuron 2 centromeric (SMN2) mRNA, in Phase Ib/IIa testing by Isis and Biogen Idec Inc. (NASDAQ:BIIB)

Not applicable

Isis-SMNRx is delivered by intrathecal injection


Isis-GCCRRx, an antisense drug targeting glucocorticoid receptor (GCCR) mRNA, completed Phase I testing by Isis

Not applicable


Eteplirsen, an antisense drug targeting dystrophin (DMD) gene to induce skipping of exon 51, completed Phase IIb testing by Sarepta Therapeutics Inc. (NASDAQ:SRPT)


iCo-007, an antisense drug targeting CRAF (RAF1) mRNA, in Phase II testing by iCo Therapeutics Inc. (TSX-V:ICO; OTCQX:ICOTF)

Bevasiranib, an siRNA drug targeting VEGF mRNA, developed by Acuity Pharmaceuticals, which became Opko Health Inc. (NYSE:OPK; Tel Aviv:OPK). The drug was acquired by RXi Pharmaceuticals Corp. (OTCQX:RXII) in 2013. (The drug was halted in Phase III by Opko in 2009 because it was unlikely to meet primary end points.)

RXi plans to reformulate bevasiranib with its self-delivering technology

Aganirsen, an antisense drug targeting insulin receptor substrate 1 (IRS1) mRNA, in Phase III testing by Gene Signal International S.A.

Not applicable

Not applicable


ATL1102, an antisense drug targeting integrin α4 (VLA-4; CD49D) mRNA, completed Phase IIa testing by Antisense Therapeutics Ltd. (ASX:ANP) and Isis

PNT2258, a nucleic acid drug targeting B cell lymphoma 2 (BCL-2; BCL2) gene to block transcription, in Phase II testing by ProNAi Therapeutics Inc.

PNT2258 is formulated in liposomes


EXC 001, an antisense drug targeting connective tissue growth factor (CTGF) mRNA, completed Phase II testing by Pfizer Inc. (NYSE:PFE)

RXI-109, an siRNA drug targeting CTGF mRNA, in Phase II testing by RXi

RXI-109 is formulated with RXi's self-delivering technology


Not applicable

QPI-1002, an siRNA drug targeting p53 mRNA, in Phase II testing by Quark Pharmaceuticals Inc., a wholly owned subsidiary of SBI Biotech Co. Ltd., and Novartis AG (NYSE:NVS; SIX:NOVN)

QPI-1002 is naked siRNA



Custirsen, an antisense drug targeting clusterin (CLU; APOJ) mRNA, in Phase III testing by OncoGenex Pharmaceuticals Inc. (NASDAQ:OGXI) and Teva Pharmaceutical Industries Ltd. (NYSE:TEVA)

Not applicable

Not applicable



Pancreas (cancer)

Not applicable

siG12D LODER, an siRNA drug targeting K-Ras (KRAS) G12D mRNA, completed Phase I/II testing by Silenseed Ltd.

siG12D LODER is formulated for slow release and is injected by endoscopic ultrasound biopsy



Custirsen is in Phase II testing by OncoGenex and Teva

Not applicable

Not applicable

Solid tumors

PNT2258 is in Phase II testing by ProNAi

CALAA-01, an siRNA drug targeting ribonucleotide reductase M2 (RRM2; R2) mRNA, in Phase Ib testing by Calando Pharmaceuticals Inc. unit of Arrowhead Research Corp. (NASDAQ:ARWR)

CALAA-01 is formulated as a transferrin receptor (TFRC; TFR)-targeted nanoparticle

Gastrointestinal neuroendocrine tumors; adrenocortical carcinoma

 Not applicable

TKM-PLK1, an siRNA drug targeting polo-like kinase 1 (PLK1; STPK13), in Phase II testing by Tekmira Pharmaceuticals Corp. (TSX:TKM; NASDAQ:TKMR)

TKM-PLK1 is formulated as a lipid nanoparticle