An overview of the clinical application of antisense oligonucleotides for RNA-targeting therapies

McClorey, Graham; Wood, Matthew

doi:10.1016/j.coph.2015.07.005

Cited by 116 publications

(93 citation statements)

References 36 publications

(35 reference statements)

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“…Finally, on the horizon are second-generation antisense oligonucleotides: small double-stranded RNA molecules that can interfere with translation by effecting efficient cleavage of target-specific mRNA [46]. A clinical trial using a factor XI antisense oligonucleotide (FXI ASO) showed the utility of this strategy to prevent postoperative deep vein thrombosis (DVT) in patients undergoing total knee replacement, and more importantly, showed that the bleeding profile in patients undergoing surgery was also acceptable [47].…”

Section: Nonwarfarin Oral Anticoagulantsmentioning

confidence: 99%

Anticoagulation for prosthetic heart valves

Yanagawa

Whitlock

Verma

et al. 2016

Current Opinion in Cardiology

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Section: Nonwarfarin Oral Anticoagulantsmentioning

confidence: 99%

Anticoagulation for prosthetic heart valves

Yanagawa

Whitlock

Verma

et al. 2016

Current Opinion in Cardiology

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“…Landmark achievements in the therapeutic development of oligonucleotides have included 1) the ability to synthesize kilogram quantities of oligonucleotide at costs that are compatible with clinical application 14 , 2) the demonstration that chemical modifications can reduce off-target effects (see below), lower toxicity, and improve pharmacokinetic properties 7,15 , 3) the demonstration that synthetic nucleic acids can be administered systemically and knock down their intended targets in vivo 7,15 ; and 4) the FDA approval of two synthetic oligonucleotides designed to target mRNA and numerous ongoing trials 16-18 .…”

Section: Targeting Mrna: Principles and Lessons Learnedmentioning

confidence: 99%

Non-coding RNAs as drug targets

Matsui

Corey

2016

Nat Rev Drug Discov

799

602

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Most of the human genome encodes RNA that does not code for protein. These noncoding RNAs (ncRNAs) may affect normal gene expression and disease progression, making them a new class of targets for drug discovery. Because their mechanisms of action are often novel, developing drugs targeting ncRNAs will involve equally novel challenges. However, many potential problems may already have been solved during development of technologies to target mRNA. Here, we will discuss the growing field of ncRNA – including microRNA, intronic RNA, repetitive RNA and long non-coding RNA - and assess the potential and challenges in their therapeutic exploitation.

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“…Two synthetic oligonucleotides have been approved by FDA and numerous ASO-based clinical trials are ongoing (173). At least 25 RNAi-based drug candidates are under clinical evaluation (174).…”

Section: Therapeutic Aspectsmentioning

confidence: 99%

Long Non-coding RNAs and their Role in Metastasis

Weidle

Birzele

Kollmorgen

et al. 2017

CGP

168

123

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Abstract.Metastasis is the major cause of death in patients with cancer. It is mediated by a multi-step process referred to as the metastatic cascade (1, 2). Initial steps include local invasion and migration, angiogenesis, epithelialmesenchymal transition (EMT) and intravasation. Tumor cells enter the circulation as single cells or circulating tumor cell clusters, are coated by platelets to escape an immune response and subsequently arrest in capillaries in distant organs as a prerequisite for extravasation. Colonization starts by homing of tumor cells in supporting niches of the organ parenchyma, followed by a latency phase which can last from several months to decades. A prerequiste for overt outgrowth of micrometastases is their adaptation to the local microenvironment and acquisition of colonisation-promoting traits (3-6). The pattern of colonized distant organs depends on the tumor type and can range from predominant spread to one organ and colonization of different types of organs sequentially or simultaneously (7). Several genes and their products have been identified to mediate crucial steps of the metastatic process such as metastasis initiation and progression, as well as organ-specific functions of metastasis (virulence) (8, 9). These gene products include proteases, chemokines, cytokines and their receptors, angiogenic factors, intracellular and transmembrane kinases, adhesion molecules, components of the extracellular matrix (ECM), GPI-linked receptors and carbohydrate metabolism-related enzymes (8, 9). More recently, an important impact of RNA-related molecules for metastasis has emerged. MicroRNAs (miRs) and other types of RNA modulate metastasis via regulatory networks (10,11). In this review we focus on the role of long non-coding RNAs (lncRNA) as promoters or inhibitors of metastasis in different tumor entities since there is an urgent need to define new targets for therapeutic intervention. With the exception of denosumab for treatment of bone metastases, all other agents evaluated in clinical studies for treatment of metastatic disease gave rise to mixed or disappointing results (6).

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An overview of the clinical application of antisense oligonucleotides for RNA-targeting therapies

Cited by 116 publications

References 36 publications

Anticoagulation for prosthetic heart valves

Anticoagulation for prosthetic heart valves

Non-coding RNAs as drug targets

Long Non-coding RNAs and their Role in Metastasis

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