Antisense oligonucleotides: the next frontier for treatment of neurological disorders

How the discovery of ISS-N1 led to the first medical therapy for spinal muscular atrophy

(2017) N N Singh et al.   GENE THERAPY

Control of phosphorothioate stereochemistry substantially increases the efficacy of antisense oligonucleotides

(2017) Naoki Iwamoto et al.   NATURE BIOTECHNOLOGY

Tau reduction prevents neuronal loss and reverses pathological tau deposition and seeding in mice with tauopathy

(2017) Sarah L. DeVos et al.   Science Translational Medicine

The Role of Dipeptide Repeats in C9ORF72-Related ALS-FTD

(2017) Brian D. Freibaum et al.   Frontiers in Molecular Neuroscience

Peptides for nucleic acid delivery

(2016) Taavi Lehto et al.   ADVANCED DRUG DELIVERY REVIEWS

Approving a Problematic Muscular Dystrophy Drug

(2016) Aaron S. Kesselheim et al.   JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION

Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study

(2016) Richard S Finkel et al.   LANCET

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

Increased 4R-Tau Induces Pathological Changes in a Human-Tau Mouse Model

(2016) Kathleen M. Schoch et al.   NEURON

Gain of Toxicity from ALS/FTD-Linked Repeat Expansions in C9ORF72 Is Alleviated by Antisense Oligonucleotides Targeting GGGGCC-Containing RNAs

(2016) Jie Jiang et al.   NEURON

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

Splice-switching antisense oligonucleotides as therapeutic drugs

(2016) Mallory A. Havens et al.   NUCLEIC ACIDS RESEARCH

The delivery of therapeutic oligonucleotides

(2016) Rudolph L. Juliano   NUCLEIC ACIDS RESEARCH

No Overt Deficits in Aged Tau-Deficient C57Bl/6.Mapttm1(EGFP)Kit GFP Knockin Mice

(2016) Annika van Hummel et al.   PLoS One

Systemic peptide-mediated oligonucleotide therapy improves long-term survival in spinal muscular atrophy

(2016) Suzan M. Hammond et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

The C9orf72 repeat expansion itself is methylated in ALS and FTLD patients

(2015) Zhengrui Xi et al.   ACTA NEUROPATHOLOGICA

Cellular uptake and intracellular trafficking of oligonucleotides

(2015) R.L. Juliano et al.   ADVANCED DRUG DELIVERY REVIEWS

Antisense oligonucleotides in therapy for neurodegenerative disorders

(2015) Melvin M. Evers et al.   ADVANCED DRUG DELIVERY REVIEWS

The Pathogenesis and Therapy of Muscular Dystrophies

(2015) Simon Guiraud et al.   Annual Review of Genomics and Human Genetics

siRNA-Loaded Polyion Complex Micelle Decorated with Charge-Conversional Polymer Tuned to Undergo Stepwise Response to Intra-Tumoral and Intra-Endosomal pHs for Exerting Enhanced RNAi Efficacy

(2015) Montira Tangsangasaksri et al.   BIOMACROMOLECULES

The TREAT-NMD DMD Global Database: Analysis of More than 7,000 Duchenne Muscular Dystrophy Mutations

(2015) Catherine L. Bladen et al.   HUMAN MUTATION

In vivo kinetic approach reveals slow SOD1 turnover in the CNS

(2015) Matthew J. Crisp et al.   JOURNAL OF CLINICAL INVESTIGATION

High-throughput screening identifies small molecules that enhance the pharmacological effects of oligonucleotides

(2015) B. Yang et al.   NUCLEIC ACIDS RESEARCH

Gene therapy and peripheral nerve repair: a perspective

(2015) Stefan A. Hoyng et al.   Frontiers in Molecular Neuroscience

In Silico Screening Based on Predictive Algorithms as a Design Tool for Exon Skipping Oligonucleotides in Duchenne Muscular Dystrophy

(2015) Yusuke Echigoya et al.   PLoS One

Mechanisms of toxicity in C9FTLD/ALS

(2014) Tania F. Gendron et al.   ACTA NEUROPATHOLOGICA

C9orf72 hypermethylation protects against repeat expansion-associated pathology in ALS/FTD

(2014) Elaine Y. Liu et al.   ACTA NEUROPATHOLOGICA

Phosphorodiamidate morpholino oligomers suppress mutant huntingtin expression and attenuate neurotoxicity

(2014) Xin Sun et al.   HUMAN MOLECULAR GENETICS

Safety and efficacy of drisapersen for the treatment of Duchenne muscular dystrophy (DEMAND II): an exploratory, randomised, placebo-controlled phase 2 study

(2014) Thomas Voit et al.   LANCET NEUROLOGY

Seizure resistance without parkinsonism in aged mice after tau reduction

(2014) Zhiyong Li et al.   NEUROBIOLOGY OF AGING

CD49d antisense drug ATL1102 reduces disease activity in patients with relapsing-remitting MS

(2014) V. Limmroth et al.   NEUROLOGY

A systematic review and meta-analysis on the epidemiology of Duchenne and Becker muscular dystrophy

(2014) Jean K. Mah et al.   NEUROMUSCULAR DISORDERS

Identification of the endosomal sorting complex required for transport-I (ESCRT-I) as an important modulator of anti-miR uptake by cancer cells

(2014) Timothy R. Wagenaar et al.   NUCLEIC ACIDS RESEARCH

The RNase H-like superfamily: new members, comparative structural analysis and evolutionary classification

(2014) Karolina A. Majorek et al.   NUCLEIC ACIDS RESEARCH

Nanoparticle Delivery of Antisense Oligonucleotides and Their Application in the Exon Skipping Strategy for Duchenne Muscular Dystrophy

(2014) Maria Sofia Falzarano et al.   Nucleic Acid Therapeutics

Antisense-mediated Exon Skipping Decreases Tau Protein Expression: A Potential Therapy For Tauopathies

(2014) Reeteka Sud et al.   Molecular Therapy-Nucleic Acids

Hypermethylation of the CpG Island Near the G4C2 Repeat in ALS with a C9orf72 Expansion

(2013) Zhengrui Xi et al.   AMERICAN JOURNAL OF HUMAN GENETICS

Eteplirsen for the treatment of Duchenne muscular dystrophy

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

A Novel Morpholino Oligomer Targeting ISS-N1 Improves Rescue of Severe Spinal Muscular Atrophy Transgenic Mice

(2013) Haiyan Zhou et al.   HUMAN GENE THERAPY

Repeat-associated non-ATG (RAN) translation in neurological disease

(2013) J. D. Cleary et al.   HUMAN MOLECULAR GENETICS

An antisense oligonucleotide against SOD1 delivered intrathecally for patients with SOD1 familial amyotrophic lateral sclerosis: a phase 1, randomised, first-in-man study

(2013) Timothy M Miller et al.   LANCET NEUROLOGY

Age-appropriate cognition and subtle dopamine-independent motor deficits in aged Tau knockout mice

(2013) Meaghan Morris et al.   NEUROBIOLOGY OF AGING

RNA Toxicity from the ALS/FTD C9ORF72 Expansion Is Mitigated by Antisense Intervention

(2013) Christopher J. Donnelly et al.   NEURON

Converging Mechanisms in ALS and FTD: Disrupted RNA and Protein Homeostasis

(2013) Shuo-Chien Ling et al.   NEURON

Antisense Oligonucleotides: Treating Neurodegeneration at the Level of RNA

(2013) Sarah L. DeVos et al.   Neurotherapeutics

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

Targeted degradation of sense and antisense C9orf72 RNA foci as therapy for ALS and frontotemporal degeneration

(2013) C. Lagier-Tourenne et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Characterization of Target mRNA Reduction Through In Situ RNA Hybridization in Multiple Organ Systems Following Systemic Antisense Treatment in Animals

(2013) Gene Hung et al.   Nucleic Acid Therapeutics

More than a bystander: the contributions of intrinsic skeletal muscle defects in motor neuron diseases

(2013) Justin G. Boyer et al.   Frontiers in Physiology

Brain pathology of spinocerebellar ataxias

(2012) Kay Seidel et al.   ACTA NEUROPATHOLOGICA

Clinical pharmacological properties of mipomersen (Kynamro), a second generation antisense inhibitor of apolipoprotein B

(2012) Stanley T. Crooke et al.   BRITISH JOURNAL OF CLINICAL PHARMACOLOGY

Designing Chemically Modified Oligonucleotides for Targeted Gene Silencing

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

Clinical pharmacokinetics of second generation antisense oligonucleotides

(2012) Rosie Z Yu et al.   Expert Opinion on Drug Metabolism & Toxicology

Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study

(2012) Elisa Majounie et al.   LANCET NEUROLOGY

RNA-mediated toxicity in neurodegenerative disease

(2012) Veronique V. Belzil et al.   MOLECULAR AND CELLULAR NEUROSCIENCE

Targeted Delivery of siRNA into Breast Cancer Cells via Phage Fusion Proteins

(2012) Deepa Bedi et al.   MOLECULAR PHARMACEUTICS

Assessing unintended hybridization-induced biological effects of oligonucleotides

(2012) Morten Lindow et al.   NATURE BIOTECHNOLOGY

Tau deficiency induces parkinsonism with dementia by impairing APP-mediated iron export

(2012) Peng Lei et al.   NATURE MEDICINE

Sustained Therapeutic Reversal of Huntington's Disease by Transient Repression of Huntingtin Synthesis

(2012) Holly B. Kordasiewicz et al.   NEURON

Global mapping of translation initiation sites in mammalian cells at single-nucleotide resolution

(2012) S. Lee et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Antisense oligonucleotide therapeutics for inherited neurodegenerative diseases

(2012) Amber L. Southwell et al.   TRENDS IN MOLECULAR MEDICINE

SOD1 in Cerebral Spinal Fluid as a Pharmacodynamic Marker for Antisense Oligonucleotide Therapy

(2012) Leah Winer et al.   JAMA Neurology

Cellular Uptake and Intracellular Trafficking of Antisense and siRNA Oligonucleotides

(2011) Rudolph L. Juliano et al.   BIOCONJUGATE CHEMISTRY

A single administration of morpholino antisense oligomer rescues spinal muscular atrophy in mouse

(2011) Paul N. Porensky et al.   HUMAN MOLECULAR GENETICS

Toll-like Receptors and Their Crosstalk with Other Innate Receptors in Infection and Immunity

(2011) Taro Kawai et al.   IMMUNITY

Exon skipping and dystrophin restoration in patients with Duchenne muscular dystrophy after systemic phosphorodiamidate morpholino oligomer treatment: an open-label, phase 2, dose-escalation study

(2011) Sebahattin Cirak et al.   LANCET

A C9orf72 promoter repeat expansion in a Flanders-Belgian cohort with disorders of the frontotemporal lobar degeneration-amyotrophic lateral sclerosis spectrum: a gene identification study

(2011) Ilse Gijselinck et al.   LANCET NEUROLOGY

Potent and Selective Antisense Oligonucleotides Targeting Single-Nucleotide Polymorphisms in the Huntington Disease Gene / Allele-Specific Silencing of Mutant Huntingtin

(2011) Jeffrey B Carroll et al.   MOLECULAR THERAPY

Pip5 Transduction Peptides Direct High Efficiency Oligonucleotide-mediated Dystrophin Exon Skipping in Heart and Phenotypic Correction in mdx Mice

(2011) HaiFang Yin et al.   MOLECULAR THERAPY

Peripheral SMN restoration is essential for long-term rescue of a severe spinal muscular atrophy mouse model

(2011) Yimin Hua et al.   NATURE

Targeting RNA to treat neuromuscular disease

(2011) Francesco Muntoni et al.   NATURE REVIEWS DRUG DISCOVERY

Expanded GGGGCC Hexanucleotide Repeat in Noncoding Region of C9ORF72 Causes Chromosome 9p-Linked FTD and ALS

(2011) Mariely DeJesus-Hernandez et al.   NEURON

A Hexanucleotide Repeat Expansion in C9ORF72 Is the Cause of Chromosome 9p21-Linked ALS-FTD

(2011) Alan E. Renton et al.   NEURON

Systemic Administration of PRO051 in Duchenne's Muscular Dystrophy

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

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

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

Long-Term Systemic Administration of Unconjugated Morpholino Oligomers for Therapeutic Expression of Dystrophin by Exon Skipping in Skeletal Muscle: Implications for Cardiac Muscle Integrity

(2011) Alberto Malerba et al.   Nucleic Acid Therapeutics

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

(2010) Keith T. Gagnon et al.   BIOCHEMISTRY

Allele-Selective Inhibition of Huntingtin Expression by Switching to an miRNA-like RNAi Mechanism

(2010) Jiaxin Hu et al.   CHEMISTRY & BIOLOGY

Antisense correction of SMN2 splicing in the CNS rescues necrosis in a type III SMA mouse model

(2010) Y. Hua et al.   GENES & DEVELOPMENT

CUGBP1 overexpression in mouse skeletal muscle reproduces features of myotonic dystrophy type 1

(2010) Amanda J. Ward et al.   HUMAN MOLECULAR GENETICS

Heart-specific overexpression of CUGBP1 reproduces functional and molecular abnormalities of myotonic dystrophy type 1

(2010) Misha Koshelev et al.   HUMAN MOLECULAR GENETICS

Endosomal escape pathways for delivery of biologicals

(2010) Amir K. Varkouhi et al.   JOURNAL OF CONTROLLED RELEASE

Preclinical PK and PD Studies on 2′-O-Methyl-phosphorothioate RNA Antisense Oligonucleotides in the mdx Mouse Model

(2010) Hans Heemskerk et al.   MOLECULAR THERAPY

Aberrant alternative splicing and extracellular matrix gene expression in mouse models of myotonic dystrophy

(2010) Hongqing Du et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Comparative analysis of antisense oligonucleotide sequences targeting exon 53 of the human DMD gene: Implications for future clinical trials

(2010) Linda J. Popplewell et al.   NEUROMUSCULAR DISORDERS

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

Non-ATG-initiated translation directed by microsatellite expansions

(2010) T. Zu et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

CAG Expansion in the Huntington Disease Gene Is Associated with a Specific and Targetable Predisposing Haplogroup

(2009) Simon C. Warby et al.   AMERICAN JOURNAL OF HUMAN GENETICS

Pathogenic mechanisms of myotonic dystrophy

(2009) Johanna E. Lee et al.   BIOCHEMICAL SOCIETY TRANSACTIONS

Five siRNAs Targeting Three SNPs May Provide Therapy for Three-Quarters of Huntington's Disease Patients

(2009) Edith L. Pfister et al.   CURRENT BIOLOGY

A majority of Huntington's disease patients may be treatable by individualized allele-specific RNA interference

(2009) Maria Stella Lombardi et al.   EXPERIMENTAL NEUROLOGY

Antisense oligonucleotide pharmacokinetics and metabolism

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

Alternating 2′-O-ribose methylation is a universal approach for generating non-stimulatory siRNA by acting as TLR7 antagonist

(2009) Svetlana Hamm et al.   IMMUNOBIOLOGY

In vivocomparison of 2′-O-methyl phosphorothioate and morpholino antisense oligonucleotides for Duchenne muscular dystrophy exon skipping

(2009) Hans A. Heemskerk et al.   JOURNAL OF GENE MEDICINE

Oligonucleotide-Mediated Survival of Motor Neuron Protein Expression in CNS Improves Phenotype in a Mouse Model of Spinal Muscular Atrophy

(2009) J. H. Williams et al.   JOURNAL OF NEUROSCIENCE

Local restoration of dystrophin expression with the morpholino oligomer AVI-4658 in Duchenne muscular dystrophy: a single-blind, placebo-controlled, dose-escalation, proof-of-concept study

(2009) Maria Kinali et al.   LANCET NEUROLOGY

Design of Phosphorodiamidate Morpholino Oligomers (PMOs) for the Induction of Exon Skipping of the Human DMD Gene

(2009) Linda J Popplewell et al.   MOLECULAR THERAPY

Allele-specific silencing of mutant huntingtin and ataxin-3 genes by targeting expanded CAG repeats in mRNAs

(2009) Jiaxin Hu et al.   NATURE BIOTECHNOLOGY

In vivo delivery of siRNA to immune cells by conjugation to a TLR9 agonist enhances antitumor immune responses

(2009) Marcin Kortylewski et al.   NATURE BIOTECHNOLOGY

Spinal muscular atrophy: why do low levels of survival motor neuron protein make motor neurons sick?

(2009) Arthur H. M. Burghes et al.   NATURE REVIEWS NEUROSCIENCE

siRNA and Innate Immunity

(2009) Marjorie Robbins et al.   OLIGONUCLEOTIDES

Triplet-repeat oligonucleotide-mediated reversal of RNA toxicity in myotonic dystrophy

(2009) S. A. M. Mulders et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Upstream open reading frames cause widespread reduction of protein expression and are polymorphic among humans

(2009) S. E. Calvo et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Reversal of RNA Dominance by Displacement of Protein Sequestered on Triplet Repeat RNA

(2009) T. M. Wheeler et al.   SCIENCE

Cross-species comparison of in vivo PK/PD relationships for second-generation antisense oligonucleotides targeting apolipoprotein B-100

(2008) Rosie Z. Yu et al.   BIOCHEMICAL PHARMACOLOGY

Identification and Allele-Specific Silencing of the Mutant Huntingtin Allele in Huntington's Disease Patient-Derived Fibroblasts

(2008) P.H.J. van Bilsen et al.   HUMAN GENE THERAPY

Emergent Dilated Cardiomyopathy Caused by Targeted Repair of Dystrophic Skeletal Muscle

(2008) DeWayne Townsend et al.   MOLECULAR THERAPY

Sustained Dystrophin Expression Induced by Peptide-conjugated Morpholino Oligomers in the Muscles of mdx Mice

(2008) Natee Jearawiriyapaisarn et al.   MOLECULAR THERAPY

Expanded CTG repeats within the DMPK 3' UTR causes severe skeletal muscle wasting in an inducible mouse model for myotonic dystrophy

(2008) J. P. Orengo et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Effective rescue of dystrophin improves cardiac function in dystrophin-deficient mice by a modified morpholino oligomer

(2008) B. Wu et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

An 8-year review of barium studies in the diagnosis of gastroparesis

(2007) A.A. Levin et al.   CLINICAL RADIOLOGY

Protein therapeutics: a summary and pharmacological classification

(2007) Benjamin Leader et al.   NATURE REVIEWS DRUG DISCOVERY