The chemical evolution of oligonucleotide therapies of clinical utility

Oligonucleotide therapies for disorders of the nervous system

(2017) Olga Khorkova et al.   NATURE BIOTECHNOLOGY

Oligonucleotide Therapeutics — A New Class of Cholesterol-Lowering Drugs

(2017) Anastasia Khvorova   NEW ENGLAND JOURNAL OF MEDICINE

A Highly Durable RNAi Therapeutic Inhibitor of PCSK9

(2017) Kevin Fitzgerald et al.   NEW ENGLAND JOURNAL OF MEDICINE

Synergistic effect of phosphorothioate, 5′-vinylphosphonate and GalNAc modifications for enhancing activity of synthetic siRNA

(2016) Thazha P. Prakash et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

5′-(E)-Vinylphosphonate: A Stable Phosphate Mimic Can Improve the RNAi Activity of siRNA-GalNAc Conjugates

(2016) Rubina Parmar et al.   CHEMBIOCHEM

The Medicinal Chemistry of Therapeutic Oligonucleotides

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

Structural Basis of Duplex Thermodynamic Stability and Enhanced Nuclease Resistance of 5′-C-Methyl Pyrimidine-Modified Oligonucleotides

(2016) Alexander V. Kel′in et al.   JOURNAL OF ORGANIC CHEMISTRY

Structural Analysis of Human Argonaute-2 Bound to a Modified siRNA Guide

(2016) Nicole T. Schirle et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Big win possible for Ionis/Biogen antisense drug in muscular atrophy

(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

The delivery of therapeutic oligonucleotides

(2016) Rudolph L. Juliano   NUCLEIC ACIDS RESEARCH

From the RNA world to the clinic

(2016) B. A. Sullenger et al.   SCIENCE

Activating frataxin expression by repeat-targeted nucleic acids

(2016) Liande Li et al.   Nature Communications

Disposition and Pharmacokinetics of a GalNAc3-Conjugated Antisense Oligonucleotide Targeting Human Lipoprotein (a) in Monkeys

(2016) Rosie Z. Yu et al.   Nucleic Acid Therapeutics

Disposition and Pharmacology of a GalNAc3-conjugated ASO Targeting Human Lipoprotein (a) in Mice

(2016) Rosie Z Yu et al.   Molecular Therapy-Nucleic Acids

Docosahexaenoic Acid Conjugation Enhances Distribution and Safety of siRNA upon Local Administration in Mouse Brain

(2016) Mehran Nikan et al.   Molecular Therapy-Nucleic Acids

siRNAmod: A database of experimentally validated chemically modified siRNAs

(2016) Showkat Ahmad Dar et al.   Scientific Reports

Ribonuclease H1-dependent hepatotoxicity caused by locked nucleic acid-modified gapmer antisense oligonucleotides

(2016) Takeshi Kasuya et al.   Scientific Reports

siRNA Conjugates Carrying Sequentially Assembled Trivalent N-Acetylgalactosamine Linked Through Nucleosides Elicit Robust Gene Silencing In Vivo in Hepatocytes

(2015) Shigeo Matsuda et al.   ACS Chemical Biology

Pharmacokinetics, biodistribution and cell uptake of antisense oligonucleotides

(2015) Richard S. Geary et al.   ADVANCED DRUG DELIVERY REVIEWS

Single-Molecule Imaging Reveals that Argonaute Reshapes the Binding Properties of Its Nucleic Acid Guides

(2015) William E. Salomon et al.   CELL

Hepatocyte-Specific Delivery of siRNAs Conjugated to Novel Non-nucleosidic TrivalentN-Acetylgalactosamine Elicits Robust Gene Silencing in Vivo

(2015) Kallanthottathil G. Rajeev et al.   CHEMBIOCHEM

Oligonucleotide therapeutics: chemistry, delivery and clinical progress

(2015) Vivek K Sharma et al.   Future Medicinal Chemistry

Antisense oligonucleotide–directed inhibition of nonsense-mediated mRNA decay

(2015) Tomoki T Nomakuchi et al.   NATURE BIOTECHNOLOGY

An RNAi therapeutic targeting antithrombin to rebalance the coagulation system and promote hemostasis in hemophilia

(2015) Alfica Sehgal et al.   NATURE MEDICINE

Cellular localization of long non-coding RNAs affects silencing by RNAi more than by antisense oligonucleotides

(2015) Kim A. Lennox et al.   NUCLEIC ACIDS RESEARCH

Enhancing antisense efficacy with multimers and multi-targeting oligonucleotides (MTOs) using cleavable linkers

(2015) Romesh R. Subramanian et al.   NUCLEIC ACIDS RESEARCH

Identification of metabolically stable 5′-phosphate analogs that support single-stranded siRNA activity

(2015) Thazha P. Prakash et al.   NUCLEIC ACIDS RESEARCH

In silicoandin vitroevaluation of exonic and intronic off-target effects form a critical element of therapeutic ASO gapmer optimization

(2015) Piotr J. Kamola et al.   NUCLEIC ACIDS RESEARCH

Hepatotoxicity of high affinity gapmer antisense oligonucleotides is mediated by RNase H1 dependent promiscuous reduction of very long pre-mRNA transcripts

(2015) Sebastien A. Burel 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

Allele-Selective Inhibition of Mutant Huntingtin with 2-Thio- and C5- Triazolylphenyl-Deoxythymidine-Modified Antisense Oligonucleotides

(2015) Michael E. Østergaard et al.   Nucleic Acid Therapeutics

Hydrophobically Modified siRNAs Silence Huntingtin mRNA in Primary Neurons and Mouse Brain

(2015) Julia F Alterman et al.   Molecular Therapy-Nucleic Acids

Synthesis of multi-galactose-conjugated 2′-O-methyl oligoribonucleotides and their in vivo imaging with positron emission tomography

(2014) Jussi Mäkilä et al.   BIOORGANIC & MEDICINAL CHEMISTRY

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

In Vivo Evaluation of Candidate Allele-specific Mutant Huntingtin Gene Silencing Antisense Oligonucleotides

(2014) Amber L Southwell et al.   MOLECULAR THERAPY

Therapeutic targeting of microRNAs: current status and future challenges

(2014) Zhonghan Li et al.   NATURE REVIEWS DRUG DISCOVERY

Systematic evaluation of antibody-mediated siRNA delivery using an industrial platform of THIOMAB–siRNA conjugates

(2014) Trinna L. Cuellar et al.   NUCLEIC ACIDS RESEARCH

Targeted delivery of antisense oligonucleotides to hepatocytes using triantennaryN-acetyl galactosamine improves potency 10-fold in mice

(2014) Thazha P. Prakash et al.   NUCLEIC ACIDS RESEARCH

Structural basis for microRNA targeting

(2014) N. T. Schirle et al.   SCIENCE

10th Annual Meeting of the Oligonucleotide Therapeutics Society

(2014) Keith T. Gagnon et al.   Nucleic Acid Therapeutics

Quantum Mechanical Studies of DNA and LNA

(2014) Troels Koch et al.   Nucleic Acid Therapeutics

Phosphorothioates, Essential Components of Therapeutic Oligonucleotides

(2014) Fritz Eckstein   Nucleic Acid Therapeutics

A Kinetic Model Explains Why Shorter and Less Affine Enzyme-recruiting Oligonucleotides Can Be More Potent

(2014) Lykke Pedersen et al.   Molecular Therapy-Nucleic Acids

Eteplirsen for the treatment of Duchenne muscular dystrophy

(2013) Jerry R. Mendell et al.   ANNALS OF NEUROLOGY

Locked nucleic acid: tighter is different

(2013) Jonathan K. Watts   CHEMICAL COMMUNICATIONS

The rough endoplasmatic reticulum is a central nucleation site of siRNA-mediated RNA silencing

(2013) Lukas Stalder et al.   EMBO JOURNAL

Novel Hydrophobically Modified Asymmetric RNAi Compounds (sd-rxRNA) Demonstrate Robust Efficacy in the Eye

(2013) Michael Byrne et al.   JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS

Delivery materials for siRNA therapeutics

(2013) Rosemary Kanasty et al.   NATURE MATERIALS

Safety and Efficacy of RNAi Therapy for Transthyretin Amyloidosis

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

Rational design of antisense oligonucleotides targeting single nucleotide polymorphisms for potent and allele selective suppression of mutant Huntingtin in the CNS

(2013) Michael E. Østergaard et al.   NUCLEIC ACIDS RESEARCH

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

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

5′ Unlocked Nucleic Acid Modification Improves siRNA Targeting

(2013) Nicholas M Snead et al.   Molecular Therapy-Nucleic Acids

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

RNA-Based Therapeutics: Current Progress and Future Prospects

(2012) John C. Burnett et al.   CHEMISTRY & BIOLOGY

Designing Chemically Modified Oligonucleotides for Targeted Gene Silencing

(2012) Glen F. Deleavey et al.   CHEMISTRY & BIOLOGY

Discovering the first microRNA-targeted drug

(2012) Morten Lindow et al.   JOURNAL OF CELL BIOLOGY

Inhibition of natural antisense transcripts in vivo results in gene-specific transcriptional upregulation

(2012) Farzaneh Modarresi et al.   NATURE BIOTECHNOLOGY

siRNA-optimized Modifications for Enhanced In Vivo Activity

(2012) Denise M Kenski et al.   Molecular Therapy-Nucleic Acids

Unique Gene-Silencing and Structural Properties of 2′-Fluoro-Modified siRNAs

(2011) Muthiah Manoharan et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Stability and Mismatch Discrimination of Locked Nucleic Acid–DNA Duplexes

(2011) Richard Owczarzy et al.   BIOCHEMISTRY

An Overview of Sugar-Modified Oligonucleotides for Antisense Therapeutics

(2011) Thazha P. Prakash   CHEMISTRY & BIODIVERSITY

Antisense drug discovery and development

(2011) Tsuyoshi Yamamoto et al.   Future Medicinal Chemistry

Novel Oligonucleotides Containing Two 3′-Ends Complementary to Target mRNA Show Optimal Gene-Silencing Activity

(2011) Lakshmi Bhagat et al.   JOURNAL OF MEDICINAL CHEMISTRY

Silencing of microRNA families by seed-targeting tiny LNAs

(2011) Susanna Obad et al.   NATURE GENETICS

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

(2011) Erich Koller et al.   NUCLEIC ACIDS RESEARCH

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

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

Allele-Selective Inhibition of MutantHuntingtinExpression with Antisense Oligonucleotides Targeting the Expanded CAG Repeat

(2010) Keith T. Gagnon et al.   BIOCHEMISTRY

Structural basis for 5′-nucleotide base-specific recognition of guide RNA by human AGO2

(2010) Filipp Frank et al.   NATURE

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

(2010) Mark E. Davis et al.   NATURE

Aptamers as therapeutics

(2010) Anthony D. Keefe et al.   NATURE REVIEWS DRUG DISCOVERY

Modulation of thermal stability can enhance the potency of siRNA

(2010) H. Addepalli et al.   NUCLEIC ACIDS RESEARCH

Synergistic effects between analogs of DNA and RNA improve the potency of siRNA-mediated gene silencing

(2010) Glen F. Deleavey et al.   NUCLEIC ACIDS RESEARCH

Short locked nucleic acid antisense oligonucleotides potently reduce apolipoprotein B mRNA and serum cholesterol in mice and non-human primates

(2010) Ellen Marie Straarup et al.   NUCLEIC ACIDS RESEARCH

A Direct Comparison of Anti-microRNA Oligonucleotide Potency

(2010) Kim A. Lennox et al.   PHARMACEUTICAL RESEARCH

A randomized, double-blind, placebo-controlled study of an RNAi-based therapy directed against respiratory syncytial virus

(2010) J. DeVincenzo et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Quantitative evaluation of siRNA delivery in vivo

(2010) Y. Pei et al.   RNA

Antisense Drug Technology: Principles, Strategies, and Applications. Edited by Stanley T. Crooke.

(2009) Kees Fluiter   ChemMedChem

G3139, an Anti-Bcl-2 Antisense Oligomer That Binds Heparin-Binding Growth Factors and Collagen I, Alters In vitro Endothelial Cell Growth and Tubular Morphogenesis

(2009) C.A. Stein et al.   CLINICAL CANCER RESEARCH

2′F-Arabinonucleic acids (2′F-ANA) — History, properties, and new frontiers

(2008) Jonathan K Watts et al.   CANADIAN JOURNAL OF CHEMISTRY

Chemically modified siRNA: tools and applications

(2008) J WATTS et al.   DRUG DISCOVERY TODAY

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

Antisense transcripts are targets for activating small RNAs

(2008) Jacob C Schwartz et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY