Modulation of RNA Splicing by Oligonucleotides: Mechanisms of Action and Therapeutic Implications

Splicing-associated chromatin signatures: a combinatorial and position-dependent role for histone marks in splicing definition

(2021) E. Agirre et al.   Nature Communications

CRISPR technologies for the treatment of Duchenne muscular dystrophy

(2021) Eunyoung Choi et al.   MOLECULAR THERAPY

Novel genome-editing-based approaches to treat motor neuron diseases: Promises and challenges

(2021) Annarita Miccio et al.   MOLECULAR THERAPY

A first exon termination checkpoint preferentially suppresses extragenic transcription

(2021) Liv M. I. Austenaa et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Overcoming the challenges of tissue delivery for oligonucleotide therapeutics

(2021) Tufan Gökirmak et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

Mesyl Phosphoramidate Oligonucleotides as Potential Splice-Switching Agents: Impact of Backbone Structure on Activity and Intracellular Localization

(2021) Suzan M. Hammond et al.   Nucleic Acid Therapeutics

High Concentration of an ISS-N1-Targeting Antisense Oligonucleotide Causes Massive Perturbation of the Transcriptome

(2021) Eric William Ottesen et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

A call to arms against ultra-rare diseases

(2021) Stanley T. Crooke   NATURE BIOTECHNOLOGY

Mechanisms of Gβγ Release upon GPCR Activation

(2021) Kirill A. Martemyanov   TRENDS IN BIOCHEMICAL SCIENCES

Transcriptome-Wide Off-Target Effects of Steric-Blocking Oligonucleotides

(2021) Erle M. Holgersen et al.   Nucleic Acid Therapeutics

SnapShot: Splicing Alterations in Cancer

(2020) Mohammad Alinoor Rahman et al.   CELL

Antisense-Mediated Transcript Knockdown Triggers Premature Transcription Termination

(2020) Jong-Sun Lee et al.   MOLECULAR CELL

Directed RNase H Cleavage of Nascent Transcripts Causes Transcription Termination

(2020) Fan Lai et al.   MOLECULAR CELL

Comparison of the efficacy of MOE and PMO modifications of systemic antisense oligonucleotides in a severe SMA mouse model

(2020) Lei Sheng et al.   NUCLEIC ACIDS RESEARCH

Enhanced CRISPR-Cas9 correction of Duchenne muscular dystrophy in mice by a self-complementary AAV delivery system

(2020) Yu Zhang et al.   Science Advances

Onasemnogene Abeparvovec-xioi: Gene Therapy for Spinal Muscular Atrophy

(2020) Debra Stevens et al.   ANNALS OF PHARMACOTHERAPY

Roles and mechanisms of alternative splicing in cancer — implications for care

(2020) Sophie C. Bonnal et al.   Nature Reviews Clinical Oncology

Phosphorothioate modified oligonucleotide–protein interactions

(2020) Stanley T Crooke et al.   NUCLEIC ACIDS RESEARCH

The Interaction of Phosphorothioate Containing RNA Targeted Drugs with Proteins is a Critical Determinant of The Therapeutic Effects of These Agents

(2020) Stanley Crooke et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Therapeutic Strategies for Duchenne Muscular Dystrophy: An Update

(2020) Chengmei Sun et al.   Genes

Risdiplam: First Approval

(2020) Sohita Dhillon   DRUGS

Discovery of a CNS penetrant small molecule SMN2 splicing modulator with improved tolerability for spinal muscular atrophy

(2020) Shiori Ando et al.   Scientific Reports

Ready for Repair? Gene Editing Enters the Clinic for the Treatment of Human Disease

(2020) Martijn P.T. Ernst et al.   Molecular Therapy-Methods & Clinical Development

Gene regulation by long non-coding RNAs and its biological functions

(2020) Luisa Statello et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Multiple competing RNA structures dynamically control alternative splicing in the human ATE1 gene

(2020) Marina Kalinina et al.   NUCLEIC ACIDS RESEARCH

Hepatotoxicity following administration of onasemnogene abeparvovec (AVXS-101) for the treatment of spinal muscular atrophy

(2020) Deepa Chand et al.   JOURNAL OF HEPATOLOGY

Safety evaluation of 2′-deoxy-2′-fluoro nucleotides in GalNAc-siRNA conjugates

(2019) Maja M Janas et al.   NUCLEIC ACIDS RESEARCH

Therapeutic developments for Duchenne muscular dystrophy

(2019) Ingrid E. C. Verhaart et al.   Nature Reviews Neurology

Current Development of siRNA Bioconjugates: From Research to the Clinic

(2019) Ivan V. Chernikov et al.   Frontiers in Pharmacology

Antisense Oligonucleotide Therapies for Neurodegenerative Diseases

(2019) C. Frank Bennett et al.   Annual Review of Neuroscience

mRNA levels can be reduced by antisense oligonucleotides via no-go decay pathway

(2019) Xue-hai Liang et al.   NUCLEIC ACIDS RESEARCH

Specific inhibition of splicing factor activity by decoy RNA oligonucleotides

(2019) Polina Denichenko et al.   Nature Communications

The Pharmacokinetics of 2′-O-Methyl Phosphorothioate Antisense Oligonucleotides: Experiences from Developing Exon Skipping Therapies for Duchenne Muscular Dystrophy

(2019) Sieto Bosgra et al.   Nucleic Acid Therapeutics

Long Non-Coding RNA Expression Levels Modulate Cell-Type-Specific Splicing Patterns by Altering Their Interaction Landscape with RNA-Binding Proteins

(2019) Felipe Wendt Porto et al.   Genes

Disruption of splicing-regulatory elements using CRISPR/Cas9 rescues spinal muscular atrophy in human iPSCs and mice

(2019) Jin-Jing Li et al.   National Science Review

Modulation of the Apoptosis Gene Bcl-x Function Through Alternative Splicing

(2019) Megan Stevens et al.   Frontiers in Genetics

Regulation of Co-transcriptional Pre-mRNA Splicing by m6A through the Low-Complexity Protein hnRNPG

(2019) Katherine I. Zhou et al.   MOLECULAR CELL

Alternative Splicing Regulatory Networks: Functions, Mechanisms, and Evolution

(2019) Jernej Ule et al.   MOLECULAR CELL

Patient-Customized Oligonucleotide Therapy for a Rare Genetic Disease

(2019) Jinkuk Kim et al.   NEW ENGLAND JOURNAL OF MEDICINE

Therapeutic approaches to treat human spliceosomal diseases

(2019) Anthony B DeNicola et al.   CURRENT OPINION IN BIOTECHNOLOGY

Hybridization-mediated off-target effects of splice-switching antisense oligonucleotides

(2019) Juergen Scharner et al.   NUCLEIC ACIDS RESEARCH

RNA editing in nascent RNA affects pre-mRNA splicing

(2018) Yun-Hua Esther Hsiao et al.   GENOME RESEARCH

Two breakthrough gene-targeted treatments for spinal muscular atrophy: challenges remain

(2018) Charlotte J. Sumner et al.   JOURNAL OF CLINICAL INVESTIGATION

H3B-8800, an orally available small-molecule splicing modulator, induces lethality in spliceosome-mutant cancers

(2018) Michael Seiler et al.   NATURE MEDICINE

A brave new world of RNA-binding proteins

(2018) Matthias W. Hentze et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Eteplirsen treatment for Duchenne muscular dystrophy

(2018) Jay S. Charleston et al.   NEUROLOGY

Acute hepatotoxicity of 2′ fluoro-modified 5–10–5 gapmer phosphorothioate oligonucleotides in mice correlates with intracellular protein binding and the loss of DBHS proteins

(2018) Wen Shen et al.   NUCLEIC ACIDS RESEARCH

Splicing regulation by long noncoding RNAs

(2018) Natali Romero-Barrios et al.   NUCLEIC ACIDS RESEARCH

Inhibition of the expression of oncogene SRSF3 by blocking an exonic splicing suppressor with antisense oligonucleotides

(2018) Jihua Guo et al.   RSC Advances

RNA-Seq Analysis of an Antisense Sequence Optimized for Exon Skipping in Duchenne Patients Reveals No Off-Target Effect

(2018) Claire Domenger et al.   Molecular Therapy-Nucleic Acids

Combined Therapies for Duchenne Muscular Dystrophy to Optimize Treatment Efficacy

(2018) Gonzalo Cordova et al.   Frontiers in Genetics

Emerging Issues in AAV-Mediated In Vivo Gene Therapy

(2018) Pasqualina Colella et al.   Molecular Therapy-Methods & Clinical Development

Discovery of Risdiplam, a Selective Survival of Motor Neuron-2 (SMN2) Gene Splicing Modifier for the Treatment of Spinal Muscular Atrophy (SMA)

(2018) Hasane Ratni et al.   JOURNAL OF MEDICINAL CHEMISTRY

Therapeutic Oligonucleotides: State of the Art

(2018) C.I. Edvard Smith et al.   Annual Review of Pharmacology and Toxicology

RNA G-quadruplex secondary structure promotes alternative splicing via the RNA-binding protein hnRNPF

(2017) Huilin Huang et al.   GENES & DEVELOPMENT

Alternative splicing: the pledge, the turn, and the prestige

(2017) L. M. Gallego-Paez et al.   HUMAN GENETICS

EMT and stemness: flexible processes tuned by alternative splicing in development and cancer progression

(2017) Davide Pradella et al.   Molecular Cancer

U1 Adaptors Suppress the KRAS-MYC Oncogenic Axis in Human Pancreatic Cancer Xenografts

(2017) Ashley T. Tsang et al.   MOLECULAR CANCER THERAPEUTICS

Multilayered Control of Alternative Splicing Regulatory Networks by Transcription Factors

(2017) Hong Han et al.   MOLECULAR CELL

The determinants of alternative RNA splicing in human cells

(2017) Tatsiana V. Ramanouskaya et al.   MOLECULAR GENETICS AND GENOMICS

Successful Repeated Hepatic Gene Delivery in Mice and Non-human Primates Achieved by Sequential Administration of AAV5 ch and AAV1

(2017) Anna Majowicz et al.   MOLECULAR THERAPY

Alternative splicing as a regulator of development and tissue identity

(2017) Francisco E. Baralle et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

The Antisense Transcript SMN-AS1 Regulates SMN Expression and Is a Novel Therapeutic Target for Spinal Muscular Atrophy

(2017) Constantin d’Ydewalle et al.   NEURON

Specific G-quadruplex ligands modulate the alternative splicing of Bcl-X

(2017) Carika Weldon et al.   NUCLEIC ACIDS RESEARCH

Gene activation of SMN by selective disruption of lncRNA-mediated recruitment of PRC2 for the treatment of spinal muscular atrophy

(2017) Caroline J. Woo et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Effects of systemic multiexon skipping with peptide-conjugated morpholinos in the heart of a dog model of Duchenne muscular dystrophy

(2017) Yusuke Echigoya et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Binding to SMN2 pre-mRNA-protein complex elicits specificity for small molecule splicing modifiers

(2017) Manaswini Sivaramakrishnan et al.   Nature Communications

Eteplirsen in the treatment of Duchenne muscular dystrophy

(2017) Kenji Rowel Lim et al.   Drug Design Development and Therapy

Development of Exon Skipping Therapies for Duchenne Muscular Dystrophy: A Critical Review and a Perspective on the Outstanding Issues

(2017) Annemieke Aartsma-Rus et al.   Nucleic Acid Therapeutics

Induced-Decay of Glycine Decarboxylase Transcripts as an Anticancer Therapeutic Strategy for Non-Small-Cell Lung Carcinoma

(2017) Jing Lin et al.   Molecular Therapy-Nucleic Acids

Oligonucleotide‐induced alternative splicing of serotonin 2C receptor reduces food intake

(2016) Zhaiyi Zhang et al.   EMBO Molecular Medicine

Expression of serine/glycine metabolism-related proteins is different according to the thyroid cancer subtype

(2016) Woo Young Sun et al.   Journal of Translational Medicine

Optimization of Morpholino Antisense Oligonucleotides Targeting the Intronic Repressor Element1 in Spinal Muscular Atrophy

(2016) Erkan Y Osman et al.   MOLECULAR THERAPY

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

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

m6A: Signaling for mRNA splicing

(2016) Samir Adhikari et al.   RNA Biology

Splicing-factor alterations in cancers

(2016) Olga Anczuków et al.   RNA

Complete androgen insensitivity syndrome caused by a deep intronic pseudoexon-activating mutation in the androgen receptor gene

(2016) Johanna Känsäkoski et al.   Scientific Reports

Mechanisms and Regulation of Alternative Pre-mRNA Splicing

(2015) Yeon Lee et al.   Annual Review of Biochemistry

Correction of a Cystic Fibrosis Splicing Mutation by Antisense Oligonucleotides

(2015) Susana Igreja et al.   HUMAN MUTATION

Antisense oligonucleotide–directed inhibition of nonsense-mediated mRNA decay

(2015) Tomoki T Nomakuchi et al.   NATURE BIOTECHNOLOGY

Functional correction in mouse models of muscular dystrophy using exon-skipping tricyclo-DNA oligomers

(2015) Aurélie Goyenvalle et al.   NATURE MEDICINE

In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy

(2015) C. E. Nelson et al.   SCIENCE

Evaluation of 2’-Deoxy-2’-fluoro Antisense Oligonucleotides for Exon Skipping in Duchenne Muscular Dystrophy

(2015) Silvana M G Jirka et al.   Molecular Therapy-Nucleic Acids

U1 Adaptors for the Therapeutic Knockdown of the Oncogene Pim-1 Kinase in Glioblastoma

(2015) Ulrike Weirauch et al.   Nucleic Acid Therapeutics

Experimental Assessment of Splicing Variants Using Expression Minigenes and Comparison with In Silico Predictions

(2014) Neeraj Sharma et al.   HUMAN MUTATION

Nonsense-mediated decay as a terminating mechanism for antisense oligonucleotides

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

Differential Expression of Enzymes Associated with Serine/Glycine Metabolism in Different Breast Cancer Subtypes

(2014) Sang Kyum Kim et al.   PLoS One

Gene suppression via U1 small nuclear RNA interference (U1i) machinery using oligonucleotides containing 2′-modified-4′-thionucleosides

(2013) Yusaku Kikuchi et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Assessing the residual CFTR gene expression in human nasal epithelium cells bearing CFTR splicing mutations causing cystic fibrosis

(2013) Laia Masvidal et al.   EUROPEAN JOURNAL OF HUMAN GENETICS

Antisense Oligonucleotides for the Treatment of Spinal Muscular Atrophy

(2013) Paul N. Porensky et al.   HUMAN GENE THERAPY

Splicing-Factor Oncoprotein SRSF1 Stabilizes p53 via RPL5 and Induces Cellular Senescence

(2013) Oliver I. Fregoso et al.   MOLECULAR CELL

Dual Masking of Specific Negative Splicing Regulatory Elements Resulted in Maximal Exon 7 Inclusion of SMN2 Gene

(2013) Peng Wen Pao et al.   MOLECULAR THERAPY

Alternative splicing: a pivotal step between eukaryotic transcription and translation

(2013) Alberto R. Kornblihtt et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Alternative Splicing for Diseases, Cancers, Drugs, and Databases

(2013) Jen-Yang Tang et al.   TheScientificWorldJOURNAL

Glycine Decarboxylase Activity Drives Non-Small Cell Lung Cancer Tumor-Initiating Cells and Tumorigenesis

(2012) Wen Cai Zhang et al.   CELL

Antisense-based therapy for the treatment of spinal muscular atrophy

(2012) Frank Rigo et al.   JOURNAL OF CELL BIOLOGY

Synthetic oligonucleotides recruit ILF2/3 to RNA transcripts to modulate splicing

(2012) Frank Rigo et al.   Nature Chemical Biology

Targeting a pre-mRNA structure with bipartite antisense molecules modulates tau alternative splicing

(2012) Eleanor Peacey et al.   NUCLEIC ACIDS RESEARCH

The DMD Locus Harbours Multiple Long Non-Coding RNAs Which Orchestrate and Control Transcription of Muscle Dystrophin mRNA Isoforms

(2012) Matteo Bovolenta et al.   PLoS One

Manipulation of PK-M mutually exclusive alternative splicing by antisense oligonucleotides

(2012) Z. Wang et al.   Open Biology

Epigenetics in Alternative Pre-mRNA Splicing

(2011) Reini F. Luco et al.   CELL

RNA structure and the mechanisms of alternative splicing

(2011) C Joel McManus et al.   CURRENT OPINION IN GENETICS & DEVELOPMENT

Bifunctional RNAs Targeting the Intronic Splicing Silencer N1 Increase SMN Levels and Reduce Disease Severity in an Animal Model of Spinal Muscular Atrophy

(2011) Erkan Y Osman et al.   MOLECULAR THERAPY

Pathogenic exon-trapping by SVA retrotransposon and rescue in Fukuyama muscular dystrophy

(2011) Mariko Taniguchi-Ikeda et al.   NATURE

U1 adaptors result in reduction of multiple pre-mRNA species principally by sequestering U1snRNP

(2011) Timothy A. Vickers et al.   NUCLEIC ACIDS RESEARCH

Design principles for bifunctional targeted oligonucleotide enhancers of splicing

(2011) N. Owen et al.   NUCLEIC ACIDS RESEARCH

A Novel Splice Variant in the N-propeptide of COL5A1 Causes an EDS Phenotype with Severe Kyphoscoliosis and Eye Involvement

(2011) Sofie Symoens et al.   PLoS One

Antitumorigenic potential of STAT3 alternative splicing modulation

(2011) F. Zammarchi et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

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

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

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

Spinal muscular atrophy: mechanisms and therapeutic strategies

(2010) C. L. Lorson et al.   HUMAN MOLECULAR GENETICS

Nonsense mutation-associated Becker muscular dystrophy: interplay between exon definition and splicing regulatory elements within the DMD gene

(2010) Kevin M. Flanigan et al.   HUMAN MUTATION

Exonic Sequences Provide Better Targets for Antisense Oligonucleotides Than Splice Site Sequences in the Modulation of Duchenne Muscular Dystrophy Splicing

(2010) Annemieke Aartsma-Rus et al.   OLIGONUCLEOTIDES

No-go decay: a quality control mechanism for RNA in translation

(2010) Yuriko Harigaya et al.   Wiley Interdisciplinary Reviews-RNA

Nucleosomes are well positioned in exons and carry characteristic histone modifications

(2009) R. Andersson et al.   GENOME RESEARCH

Delivery of bifunctional RNAs that target an intronic repressor and increase SMN levels in an animal model of spinal muscular atrophy

(2009) T. D. Baughan et al.   HUMAN MOLECULAR GENETICS

XPCbranch-point sequence mutations disrupt U2 snRNP binding, resulting in abnormal pre-mRNA splicing in xeroderma pigmentosum patients

(2009) Sikandar G. Khan et al.   HUMAN MUTATION

Combination of circulating CXCR4 and Bmi-1 mRNA in plasma: A potential novel tumor marker for gastric cancer

(2009) Xu   Molecular Medicine Reports

Gene silencing by synthetic U1 Adaptors

(2009) Rafal Goraczniak et al.   NATURE BIOTECHNOLOGY

Mechanisms of alternative splicing regulation: insights from molecular and genomics approaches

(2009) Mo Chen et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Nucleosome positioning as a determinant of exon recognition

(2009) Hagen Tilgner et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Substances that can change alternative splice-site selection: Table 1

(2008) Chiranthani Sumanasekera et al.   BIOCHEMICAL SOCIETY TRANSACTIONS

Alternative splicing and disease

(2008) Jamal Tazi et al.   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

A Negatively Acting Bifunctional RNA Increases Survival Motor Neuron Both In Vitro and In Vivo

(2008) Alexa Dickson et al.   HUMAN GENE THERAPY

Multiple roles of TDP-43 in gene expression, splicing regulation, and human disease

(2007) Emanuele Buratti   Frontiers in Bioscience-Landmark