RNA Therapeutics in Oncology: Advances, Challenges, and Future Directions

A phase I dose-escalation study of apatorsen (OGX-427), an antisense inhibitor targeting heat shock protein 27 (Hsp27), in patients with castration-resistant prostate cancer and other advanced cancers

(2016) K. N. Chi et al.   ANNALS OF ONCOLOGY

Conjugation of mono and di-GalNAc sugars enhances the potency of antisense oligonucleotides via ASGR mediated delivery to hepatocytes

(2016) Garth A. Kinberger et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Current and Future Treatment Approaches in Transthyretin Familial Amyloid Polyneuropathy

(2016) Philippe Kerschen et al.   Current Treatment Options in Neurology

The therapeutic potential of new investigational hepatitis C virus translation inhibitors

(2016) Guglielmo Borgia et al.   EXPERT OPINION ON INVESTIGATIONAL DRUGS

Comprehensive Structure–Activity Relationship of Triantennary N-Acetylgalactosamine Conjugated Antisense Oligonucleotides for Targeted Delivery to Hepatocytes

(2016) Thazha P. Prakash et al.   JOURNAL OF MEDICINAL CHEMISTRY

The Medicinal Chemistry of Therapeutic Oligonucleotides

(2016) W. Brad Wan et al.   JOURNAL OF MEDICINAL CHEMISTRY

Antisense oligonucleotides targeting apolipoprotein(a) in people with raised lipoprotein(a): two randomised, double-blind, placebo-controlled, dose-ranging trials

(2016) Nicholas J Viney et al.   LANCET

Alnylam terminates revusiran program, stock plunges

(2016) Ken Garber   NATURE BIOTECHNOLOGY

Translation efficiency of mRNAs is increased by antisense oligonucleotides targeting upstream open reading frames

(2016) Xue-hai Liang et al.   NATURE BIOTECHNOLOGY

Results from a phase 1 study of nusinersen (ISIS-SMNRx) in children with spinal muscular atrophy

(2016) Claudia A. Chiriboga et al.   NEUROLOGY

Hsp90 protein interacts with phosphorothioate oligonucleotides containing hydrophobic 2′-modifications and enhances antisense activity

(2016) Xue-Hai Liang et al.   NUCLEIC ACIDS RESEARCH

RNA cleavage products generated by antisense oligonucleotides and siRNAs are processed by the RNA surveillance machinery

(2016) Walt F. Lima et al.   NUCLEIC ACIDS RESEARCH

Aberrant Splicing in Cancer: Mediators of Malignant Progression through an Imperfect Splice Program Shift

(2016) Felipe Andrés Cordero Luz et al.   ONCOLOGY

Development of a Quantitative BRET Affinity Assay for Nucleic Acid-Protein Interactions

(2016) Timothy A. Vickers et al.   PLoS One

Clinical development of TargomiRs, a miRNA mimic-based treatment for patients with recurrent thoracic cancer

(2016) Glen Reid et al.   Epigenomics

Generation 2.5 Antisense Oligonucleotides Targeting the Androgen Receptor and Its Splice Variants Suppress Enzalutamide-Resistant Prostate Cancer Cell Growth

(2015) Y. Yamamoto et al.   CLINICAL CANCER RESEARCH

No effect on QT intervals of mipomersen, a 2′-O-methoxyethyl modified antisense oligonucleotide targeting ApoB-100 mRNA, in a phase I dose escalation placebo-controlled study, and confirmed by a thorough QT (tQT) study, in healthy subjects

(2015) Rosie Z. Yu et al.   EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY

The role of clusterin in prostate cancer: treatment resistance and potential as a therapeutic target

(2015) Lateef A Muhammad et al.   Expert Review of Anticancer Therapy

Antisense oligonucleotide–directed inhibition of nonsense-mediated mRNA decay

(2015) Tomoki T Nomakuchi et al.   NATURE BIOTECHNOLOGY

Clinical experiences with systemically administered siRNA-based therapeutics in cancer

(2015) Jonathan E. Zuckerman et al.   NATURE REVIEWS DRUG DISCOVERY

Factor XI Antisense Oligonucleotide for Prevention of Venous Thrombosis

(2015) Harry R. Büller et al.   NEW ENGLAND JOURNAL OF MEDICINE

The rates of the major steps in the molecular mechanism of RNase H1-dependent antisense oligonucleotide induced degradation of RNA

(2015) Timothy A. Vickers et al.   NUCLEIC ACIDS RESEARCH

2′-Fluoro-modified phosphorothioate oligonucleotide can cause rapid degradation of P54nrb and PSF

(2015) Wen Shen et al.   NUCLEIC ACIDS RESEARCH

Efficacy and safety of patisiran for familial amyloidotic polyneuropathy: a phase II multi-dose study

(2015) Ole B Suhr et al.   Orphanet Journal of Rare Diseases

Increase of microRNA-210, Decrease of Raptor Gene Expression and Alteration of Mammalian Target of Rapamycin Regulated Proteins following Mithramycin Treatment of Human Erythroid Cells

(2015) Nicoletta Bianchi et al.   PLoS One

Analysis of 13 cell types reveals evidence for the expression of numerous novel primate- and tissue-specific microRNAs

(2015) Eric Londin et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

AZD9150, a next-generation antisense oligonucleotide inhibitor of STAT3 with early evidence of clinical activity in lymphoma and lung cancer

(2015) David Hong et al.   Science Translational Medicine

RNAi therapy targeting KRAS in combination with chemotherapy for locally advanced pancreatic cancer patients

(2015) Talia Golan et al.   Oncotarget

Genetic variants in microRNA genes: impact on microRNA expression, function, and disease

(2015) Sophia Cammaerts et al.   Frontiers in Genetics

Mipomersen is a Promising Therapy in the Management of Hypercholesterolemia: A Meta-Analysis of Randomized Controlled Trials

(2014) Na Li et al.   American Journal of Cardiovascular Drugs

Expression of microRNA-93 and Interleukin-8 duringPseudomonas aeruginosa–Mediated Induction of Proinflammatory Responses

(2014) Enrica Fabbri et al.   AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY

217 Results of a phase I, open-label, multicentre study to assess the safety, tolerability, pharmacokinetics and preliminary anti-tumour activity of AZD9150 in patients with advanced/metastatic hepatocellular carcinoma

(2014) Y.K. Kang et al.   EUROPEAN JOURNAL OF CANCER

457 Preclinical pharmacology of AZD5312, a generation 2.5 antisense oligonucletotide targeting the androgen receptor with differentiated activity from enzalutamide

(2014) B.R. Davies et al.   EUROPEAN JOURNAL OF CANCER

Multivalent N-Acetylgalactosamine-Conjugated siRNA Localizes in Hepatocytes and Elicits Robust RNAi-Mediated Gene Silencing

(2014) Jayaprakash K. Nair et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Towards a therapy for Angelman syndrome by targeting a long non-coding RNA

(2014) Linyan Meng et al.   NATURE

mRNA-based therapeutics — developing a new class of drugs

(2014) Ugur Sahin et al.   NATURE REVIEWS DRUG DISCOVERY

Targeting APOC3 in the Familial Chylomicronemia Syndrome

(2014) Daniel Gaudet et al.   NEW ENGLAND JOURNAL OF MEDICINE

Nonsense-mediated decay as a terminating mechanism for antisense oligonucleotides

(2014) Amanda J. Ward et al.   NUCLEIC ACIDS RESEARCH

YM500v2: a small RNA sequencing (smRNA-seq) database for human cancer miRNome research

(2014) Wei-Chung Cheng et al.   NUCLEIC ACIDS RESEARCH

Phosphorothioate oligonucleotides can displaceNEAT1RNA and form nuclear paraspeckle-like structures

(2014) Wen Shen et al.   NUCLEIC ACIDS RESEARCH

TCP1 complex proteins interact with phosphorothioate oligonucleotides and can co-localize in oligonucleotide-induced nuclear bodies in mammalian cells

(2014) Xue-hai Liang et al.   NUCLEIC ACIDS RESEARCH

A combinatorial microRNA therapeutics approach to suppressing non-small cell lung cancer

(2014) A L Kasinski et al.   ONCOGENE

Antisense Oligonucleotides Capable of Promoting Specific Target mRNA Reduction via Competing RNase H1-Dependent and Independent Mechanisms

(2014) Timothy A. Vickers et al.   PLoS One

Correlating animal and human phase Ia/Ib clinical data with CALAA-01, a targeted, polymer-based nanoparticle containing siRNA

(2014) J. E. Zuckerman et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Evidence for the biogenesis of more than 1,000 novel human microRNAs

(2014) Marc R Friedländer et al.   GENOME BIOLOGY

Mir-34: A New Weapon Against Cancer?

(2014) Gabriella Misso et al.   Molecular Therapy-Nucleic Acids

Restoring expression of miR-16: a novel approach to therapy for malignant pleural mesothelioma

(2013) G. Reid et al.   ANNALS OF ONCOLOGY

Hsp27 Regulates Epithelial Mesenchymal Transition, Metastasis, and Circulating Tumor Cells in Prostate Cancer

(2013) M. Shiota et al.   CANCER RESEARCH

The role of heat shock proteins in bladder cancer

(2013) Joseph Ischia et al.   Nature Reviews Urology

Safety and Efficacy of RNAi Therapy for Transthyretin Amyloidosis

(2013) Teresa Coelho et al.   NEW ENGLAND JOURNAL OF MEDICINE

Miravirsen (SPC3649) can inhibit the biogenesis of miR-122

(2013) Luca F. R. Gebert et al.   NUCLEIC ACIDS RESEARCH

Mutant KRAS is a druggable target for pancreatic cancer

(2013) E. Zorde Khvalevsky et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

First-in-Humans Trial of an RNA Interference Therapeutic Targeting VEGF and KSP in Cancer Patients with Liver Involvement

(2013) Josep Tabernero et al.   Cancer Discovery

Antisense oligonucleotides on neurobehavior, respiratory, and cardiovascular function, and hERG channel current studies

(2013) Tae-Won Kim et al.   JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS

Clinical development of an antisense therapy for the treatment of transthyretin-associated polyneuropathy

(2012) Elizabeth J. Ackermann et al.   AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS

Lipid nanoparticles for hepatic delivery of small interfering RNA

(2012) Bo Yu et al.   BIOMATERIALS

Single-Stranded RNAs Use RNAi to Potently and Allele-Selectively Inhibit Mutant Huntingtin Expression

(2012) Dongbo Yu et al.   CELL

Single-Stranded siRNAs Activate RNAi in Animals

(2012) Walt F. Lima et al.   CELL

TricycloDNA-modified oligo-2′-deoxyribonucleotides reduce scavenger receptor B1 mRNA in hepatic and extra-hepatic tissues—a comparative study of oligonucleotide length, design and chemistry

(2012) Sue Murray et al.   NUCLEIC ACIDS RESEARCH

Current progress of siRNA/shRNA therapeutics in clinical trials

(2011) John C. Burnett et al.   Biotechnology Journal

Mechanisms and role of microRNA deregulation in cancer onset and progression

(2011) Edenir Inês Palmero et al.   GENETICS AND MOLECULAR BIOLOGY

Phase I clinical development of Atu027, a siRNA formulation targeting PKN3 in patients with advanced solid tumors

(2011) Dirk Strumberg et al.   INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS

Systemic Administration of PRO051 in Duchenne's Muscular Dystrophy

(2011) Nathalie M. Goemans et al.   NEW ENGLAND JOURNAL OF MEDICINE

Mechanisms of single-stranded phosphorothioate modified antisense oligonucleotide accumulation in hepatocytes

(2011) Erich Koller et al.   NUCLEIC ACIDS RESEARCH

Antisense Oligonucleotides Delivered to the Mouse CNS Ameliorate Symptoms of Severe Spinal Muscular Atrophy

(2011) M. A. Passini et al.   Science Translational Medicine

RNA Targeting Therapeutics: Molecular Mechanisms of Antisense Oligonucleotides as a Therapeutic Platform

(2010) C. Frank Bennett et al.   Annual Review of Pharmacology and Toxicology

Thelet-7microRNA reduces tumor growth in mouse models of lung cancer

(2010) Aurora Esquela-Kerscher et al.   CELL CYCLE

Tumor Survivin Is Downregulated by the Antisense Oligonucleotide LY2181308: A Proof-of-Concept, First-in-Human Dose Study

(2010) D. C. Talbot et al.   CLINICAL CANCER RESEARCH

Mammalian microRNAs predominantly act to decrease target mRNA levels

(2010) Huili Guo et al.   NATURE

Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles

(2010) Mark E. Davis et al.   NATURE

Targeting microRNAs in cancer: rationale, strategies and challenges

(2010) Ramiro Garzon et al.   NATURE REVIEWS DRUG DISCOVERY

Targeting of mRNAs by multiple miRNAs: the next step

(2010) M E Peter   ONCOGENE

Integrative genome analysis reveals an oncomir/oncogene cluster regulating glioblastoma survivorship

(2010) H. Kim et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Cell Cycle Regulation by MicroRNAs in Embryonic Stem Cells

(2009) Y. Wang et al.   CANCER RESEARCH

miR-15a and miR-16-1 in cancer: discovery, function and future perspectives

(2009) R I Aqeilan et al.   CELL DEATH AND DIFFERENTIATION

Mechanisms of miRNA-mediated post-transcriptional regulation in animal cells

(2009) Marina Chekulaeva et al.   CURRENT OPINION IN CELL BIOLOGY

Antisense oligonucleotide pharmacokinetics and metabolism

(2009) Richard S Geary   Expert Opinion on Drug Metabolism & Toxicology

The First Targeted Delivery of siRNA in Humans via a Self-Assembling, Cyclodextrin Polymer-Based Nanoparticle: From Concept to Clinic

(2009) Mark E. Davis   MOLECULAR PHARMACEUTICS

Oncogene Addiction

(2008) I. B. Weinstein et al.   CANCER RESEARCH

A Phase I Study of OGX-011, a 2'-Methoxyethyl Phosphorothioate Antisense to Clusterin, in Combination with Docetaxel in Patients with Advanced Cancer

(2008) K. N. Chi et al.   CLINICAL CANCER RESEARCH

Short Antisense Oligonucleotides with Novel 2′−4′ Conformationaly Restricted Nucleoside Analogues Show Improved Potency without Increased Toxicity in Animals

(2008) Punit P. Seth et al.   JOURNAL OF MEDICINAL CHEMISTRY

Translating insights from the cancer genome into clinical practice

(2008) Lynda Chin et al.   NATURE

Comprehensive genomic characterization defines human glioblastoma genes and core pathways

(2008) Roger McLendon et al.   NATURE

Chemical Modification of siRNAs for In Vivo Use

(2008) Mark A. Behlke   OLIGONUCLEOTIDES

Suppression of non-small cell lung tumor development by the let-7 microRNA family

(2008) M. S. Kumar et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA