A critical analysis of methods used to investigate the cellular uptake and subcellular localization of RNA therapeutics

Golodirsen: First Approval

(2020) Young-A Heo   DRUGS

Givosiran: First Approval

(2020) Lesley J. Scott   DRUGS

Cell-Penetrating Streptavidin: A General Tool for Bifunctional Delivery with Spatiotemporal Control, Mediated by Transport Systems Such as Adaptive Benzopolysulfane Networks

(2020) Javier López-Andarias et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Efficient Delivery of Antisense Oligonucleotides Using Bioreducible Lipid Nanoparticles In Vitro and In Vivo

(2020) Liu Yang et al.   Molecular Therapy-Nucleic Acids

Cellular Uptake and Cytosolic Delivery of a Cyclic Cystine Knot Scaffold

(2020) Huawu Yin et al.   ACS Chemical Biology

Oligonucleotides: Current Trends and Innovative Applications in the Synthesis, Characterization, and Purification

(2020) Martina Catani et al.   Biotechnology Journal

RNA therapeutics on the rise

(2020) Feng Wang et al.   NATURE REVIEWS DRUG DISCOVERY

Guidelines for Experiments Using Antisense Oligonucleotides and Double-Stranded RNAs

(2019) Keith T. Gagnon et al.   Nucleic Acid Therapeutics

The current state and future directions of RNAi-based therapeutics

(2019) Ryan L. Setten et al.   NATURE REVIEWS DRUG DISCOVERY

Selective tissue targeting of synthetic nucleic acid drugs

(2019) Punit P. Seth et al.   JOURNAL OF CLINICAL INVESTIGATION

Trapped! A critical evaluation of methods for measuring total cellular uptake versus cytosolic localization

(2019) Kirsten Deprey et al.   BIOCONJUGATE CHEMISTRY

Strategies, design, and chemistry in siRNA delivery systems

(2019) Yizhou Dong et al.   ADVANCED DRUG DELIVERY REVIEWS

The valency of fatty acid conjugates impacts siRNA pharmacokinetics, distribution, and efficacy in vivo

(2019) Annabelle Biscans et al.   JOURNAL OF CONTROLLED RELEASE

Differential uptake, kinetics and mechanisms of intracellular trafficking of next-generation antisense oligonucleotides across human cancer cell lines

(2019) Emily Linnane et al.   NUCLEIC ACIDS RESEARCH

Specific Delivery of Oligonucleotides to the Cell Nucleus via Gentle Compression and Attachment of Polythymidine

(2019) Zhong Chen et al.   ACS Applied Materials & Interfaces

Observing an antisense drug complex in intact human cells by in-cell NMR

(2019) Judith Schlagnitweit et al.   CHEMBIOCHEM

Volanesorsen: First Global Approval

(2019) Julia Paik et al.   DRUGS

The nuclear concentration required for antisense oligonucleotide activity in myotonic dystrophy cells

(2019) M. Leontien van der Bent et al.   FASEB JOURNAL

Lipid Conjugates Enhance Endosomal Release of Antisense Oligonucleotides Into Cells

(2019) Shiyu Wang et al.   Nucleic Acid Therapeutics

Monitoring DNA–Ligand Interactions in Living Human Cells Using NMR Spectroscopy

(2019) Michaela Krafcikova et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Selection of DNA-Encoded Libraries to Protein Targets within and on Living Cells

(2019) Bo Cai et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Patient-Customized Oligonucleotide Therapy for a Rare Genetic Disease

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

LC–TOF–MS methods to quantify siRNAs and major metabolite in plasma, urine and tissues

(2019) Lakshmi Ramanathan et al.   Bioanalysis

Oligonucleotide quantification and metabolite profiling by high-resolution and accurate mass spectrometry

(2019) Ju Liu et al.   Bioanalysis

Importance of probe design for bioanalysis of oligonucleotides using hybridization-based LC-fluorescence assays

(2019) Yuhuan Ji et al.   Bioanalysis

Nuclear and Cytoplasmatic Quantification of Unconjugated, Label-Free Locked Nucleic Acid Oligonucleotides

(2019) Hannah Pendergraff et al.   Nucleic Acid Therapeutics

Assessing the Cell Permeability of Bivalent Chemical Degraders Using the Chloroalkane Penetration Assay

(2019) Caroline A. Foley et al.   ACS Chemical Biology

Caprin‐1 Promotes Cellular Uptake of Nucleic Acids with Backbone and Sequence Discrimination

(2019) Valentina Galli et al.   HELVETICA CHIMICA ACTA

Golgi-endosome transport mediated by M6PR facilitates release of antisense oligonucleotides from endosomes

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

Enzyme-Activated Fluorogenic Probes for Live-Cell and in Vivo Imaging

(2018) Wen Chyan et al.   ACS Chemical Biology

Evaluation of the Stability of DNA i-Motifs in the Nuclei of Living Mammalian Cells

(2018) Simon Dzatko et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Novel Cluster and Monomer-Based GalNAc Structures Induce Effective Uptake of siRNAs in Vitro and in Vivo

(2018) Vivek K. Sharma et al.   BIOCONJUGATE CHEMISTRY

Unique arginine array improves cytosolic localization of hydrocarbon-stapled peptides

(2018) Kim Quach et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Locked nucleic acid: modality, diversity, and drug discovery

(2018) Peter H. Hagedorn et al.   DRUG DISCOVERY TODAY

A randomized placebo-controlled phase 3 trial of an antisense oligonucleotide, drisapersen, in Duchenne muscular dystrophy

(2018) Nathalie Goemans et al.   NEUROMUSCULAR DISORDERS

Cellular uptake mediated by epidermal growth factor receptor facilitates the intracellular activity of phosphorothioate-modified antisense oligonucleotides

(2018) Shiyu Wang et al.   NUCLEIC ACIDS RESEARCH

Structure–activity relationships and cellular mechanism of action of small molecules that enhance the delivery of oligonucleotides

(2018) Rudolph L Juliano et al.   NUCLEIC ACIDS RESEARCH

Comparison of partially and fully chemically-modified siRNA in conjugate-mediated delivery in vivo

(2018) Matthew R Hassler et al.   NUCLEIC ACIDS RESEARCH

The first successful observation of in-cell NMR signals of DNA and RNA in living human cells

(2018) Yudai Yamaoki et al.   PHYSICAL CHEMISTRY CHEMICAL PHYSICS

Review on investigations of antisense oligonucleotides with the use of mass spectrometry

(2018) Sylwia Studzińska   TALANTA

Comparison of Cell Permeability of Cyclic Peptoids and Linear Peptoids

(2018) Min-Kyung Shin et al.   ACS Combinatorial Science

Endosomal Escape of Antisense Oligonucleotides Internalized by Stabilin Receptors Is Regulated by Rab5C and EEA1 During Endosomal Maturation

(2018) Colton M. Miller et al.   Nucleic Acid Therapeutics

Intracellular Trafficking and Endosomal Release of Oligonucleotides: What We Know and What We Don’t

(2018) R.L. Juliano   Nucleic Acid Therapeutics

Improving siRNA Delivery In Vivo Through Lipid Conjugation

(2018) Maire F. Osborn et al.   Nucleic Acid Therapeutics

Fluorophore labeling of a cell-penetrating peptide significantly alters the mode and degree of biomembrane interaction

(2018) Sofie Fogh Hedegaard et al.   Scientific Reports

Multiplexed fluorescence lifetime imaging by concentration-dependent quenching

(2018) Teng Luo et al.   Journal of Materials Chemistry B

Where in the cell is our cargo? Current methods to study intracellular cytosolic localization.

(2018) Alejandro Méndez Ardoy et al.   CHEMBIOCHEM

Inotersen: First Global Approval

(2018) Susan J. Keam   DRUGS

Patisiran: First Global Approval

(2018) Sheridan M. Hoy   DRUGS

Cell Penetration Profiling Using the Chloroalkane Penetration Assay

(2018) Leila Peraro et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

COPII vesicles can affect the activity of antisense oligonucleotides by facilitating the release of oligonucleotides from endocytic pathways

(2018) Xue-hai Liang et al.   NUCLEIC ACIDS RESEARCH

Chemical Modification Study of Antisense Gapmers

(2018) Robert Stanton et al.   Nucleic Acid Therapeutics

Systematic Screening of Commonly Used Commercial Transfection Reagents towards Efficient Transfection of Single-Stranded Oligonucleotides

(2018) Tao Wang et al.   MOLECULES

Quantitative fluorescence imaging determines the absolute number of locked nucleic acid oligonucleotides needed for suppression of target gene expression

(2018) Annette Buntz et al.   NUCLEIC ACIDS RESEARCH

Diverse lipid conjugates for functional extra-hepatic siRNA delivery in vivo

(2018) Annabelle Biscans et al.   NUCLEIC ACIDS RESEARCH

Rescue of Outer Hair Cells with Antisense Oligonucleotides in Usher Mice Is Dependent on Age of Treatment

(2017) Abhilash Ponnath et al.   JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY

Diversity-Oriented Stapling Yields Intrinsically Cell-Penetrant Inducers of Autophagy

(2017) Leila Peraro et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

RNA fluorescence in situ hybridization for high-content screening

(2017) Emmanuelle Querido et al.   METHODS

RNase H1-Dependent Antisense Oligonucleotides Are Robustly Active in Directing RNA Cleavage in Both the Cytoplasm and the Nucleus

(2017) Xue-Hai Liang et al.   MOLECULAR THERAPY

The chemical evolution of oligonucleotide therapies of clinical utility

(2017) Anastasia Khvorova et al.   NATURE BIOTECHNOLOGY

Cellular uptake and trafficking of antisense oligonucleotides

(2017) Stanley T Crooke et al.   NATURE BIOTECHNOLOGY

Nusinersen, an antisense oligonucleotide drug for spinal muscular atrophy

(2017) David R Corey   NATURE NEUROSCIENCE

Intra-endosomal trafficking mediated by lysobisphosphatidic acid contributes to intracellular release of phosphorothioate-modified antisense oligonucleotides

(2017) Shiyu Wang et al.   NUCLEIC ACIDS RESEARCH

Asialoglycoprotein receptor 1 mediates productive uptake of N-acetylgalactosamine-conjugated and unconjugated phosphorothioate antisense oligonucleotides into liver hepatocytes

(2017) Michael Tanowitz et al.   NUCLEIC ACIDS RESEARCH

5΄-Vinylphosphonate improves tissue accumulation and efficacy of conjugated siRNAs in vivo

(2017) Reka A. Haraszti et al.   NUCLEIC ACIDS RESEARCH

Nucleic acid binding proteins affect the subcellular distribution of phosphorothioate antisense oligonucleotides

(2017) Jeffrey K. Bailey et al.   NUCLEIC ACIDS RESEARCH

Evaluation of fluorescence in situ hybridization techniques to study long non-coding RNA expression in cultured cells

(2017) Ricardo J Soares et al.   NUCLEIC ACIDS RESEARCH

Chemistry, mechanism and clinical status of antisense oligonucleotides and duplex RNAs

(2017) Xiulong Shen et al.   NUCLEIC ACIDS RESEARCH

Monitoring integrity and localization of modified single-stranded RNA oligonucleotides using ultrasensitive fluorescence methods

(2017) Philipp Heissig et al.   PLoS One

SIDT2 mediates gymnosis, the uptake of naked single-stranded oligonucleotides into living cells

(2017) Masayuki Takahashi et al.   RNA Biology

Eteplirsen in the treatment of Duchenne muscular dystrophy

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

Pharmacokinetic Profiling of Conjugated Therapeutic Oligonucleotides: A High-Throughput Method Based Upon Serial Blood Microsampling Coupled to Peptide Nucleic Acid Hybridization Assay

(2017) Bruno M.D.C. Godinho et al.   Nucleic Acid Therapeutics

Intracellular Distribution and Nuclear Activity of Antisense Oligonucleotides After Unassisted Uptake in Myoblasts and Differentiated Myotubes In Vitro

(2017) Anchel González-Barriga et al.   Nucleic Acid Therapeutics

Impact of Oligonucleotide Structure, Chemistry, and Delivery Method on In Vitro Cytotoxicity

(2017) Maja M. Janas et al.   Nucleic Acid Therapeutics

Molecular Mechanisms of Antisense Oligonucleotides

(2017) Stanley T. Crooke   Nucleic Acid Therapeutics

Clinical trials of exon skipping in Duchenne muscular dystrophy

(2017) Jerry R Mendell et al.   Expert Opinion on Orphan Drugs

The Medicinal Chemistry of Therapeutic Oligonucleotides

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

Protein Kinase C-α is a Critical Protein for Antisense Oligonucleotide-mediated Silencing in Mammalian Cells

(2016) Daniela Castanotto et al.   MOLECULAR THERAPY

Stabilin-1 and Stabilin-2 are specific receptors for the cellular internalization of phosphorothioate-modified antisense oligonucleotides (ASOs) in the liver

(2016) Colton M. Miller et al.   NUCLEIC ACIDS RESEARCH

The delivery of therapeutic oligonucleotides

(2016) Rudolph L. Juliano   NUCLEIC ACIDS RESEARCH

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

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

Delivery of therapeutic oligonucleotides with cell penetrating peptides

(2015) Prisca Boisguérin et al.   ADVANCED DRUG DELIVERY REVIEWS

Efficient cell-specific uptake of binding proteins into the cytoplasm through engineered modular transport systems

(2015) Wouter P.R. Verdurmen et al.   JOURNAL OF CONTROLLED RELEASE

Fluorescence Correlation Spectroscopy Reveals Highly Efficient Cytosolic Delivery of Certain Penta-Arg Proteins and Stapled Peptides

(2015) Jonathan R. LaRochelle et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Visualizing lipid-formulated siRNA release from endosomes and target gene knockdown

(2015) Anders Wittrup et al.   NATURE BIOTECHNOLOGY

Development and Application of an Ultrasensitive Hybridization-Based ELISA Method for the Determination of Peptide-Conjugated Phosphorodiamidate Morpholino Oligonucleotides

(2015) Umar Burki et al.   Nucleic Acid Therapeutics

GFP-complementation assay to detect functional CPP and protein delivery into living cells

(2015) Nadia Milech et al.   Scientific Reports

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

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

Localized light-induced protein dimerization in living cells using a photocaged dimerizer

(2014) Edward R. Ballister et al.   Nature Communications

Cellular Uptake and Intracellular Trafficking of Oligonucleotides: Implications for Oligonucleotide Pharmacology

(2014) R.L. Juliano et al.   Nucleic Acid Therapeutics

Phosphorothioates, Essential Components of Therapeutic Oligonucleotides

(2014) Fritz Eckstein   Nucleic Acid Therapeutics

Fifteen Years of Cell-Penetrating, Guanidinium-Rich Molecular Transporters: Basic Science, Research Tools, and Clinical Applications

(2013) Erika Geihe Stanzl et al.   ACCOUNTS OF CHEMICAL RESEARCH

Lipid Nanoparticles Improve Activity of Single-Stranded siRNA and Gapmer Antisense Oligonucleotides in Animals

(2013) Thazha P. Prakash et al.   ACS Chemical Biology

Improved Assays for Determining the Cytosolic Access of Peptides, Proteins, and Their Mimetics

(2013) Justin M. Holub et al.   BIOCHEMISTRY

Mipomersen Sodium: First Global Approval

(2013) Philip Hair et al.   DRUGS

Image-based analysis of lipid nanoparticle–mediated siRNA delivery, intracellular trafficking and endosomal escape

(2013) Jerome Gilleron et al.   NATURE BIOTECHNOLOGY

Receptors, endocytosis, and trafficking: the biological basis of targeted delivery of antisense and siRNA oligonucleotides

(2012) R. L. Juliano et al.   JOURNAL OF DRUG TARGETING

Determination of cellular uptake and intracellular levels of Cenersen (Aezea®, EL625), a p53 antisense oligonucleotide in acute myeloid leukemia cells

(2012) Houda Alachkar et al.   JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS

Cellular uptake of modified oligonucleotides enhanced by porphyrins studied by time-resolved microspectrofluorimetry and fluorescence imaging techniques

(2011) P. Praus et al.   JOURNAL OF MOLECULAR STRUCTURE

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

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

Effect of dose and plasma concentration on liver uptake and pharmacologic activity of a 2′-methoxyethyl modified chimeric antisense oligonucleotide targeting PTEN

(2009) Richard S. Geary et al.   BIOCHEMICAL PHARMACOLOGY

SnapShot: Endocytic Trafficking

(2009) Marnix Wieffer et al.   CELL

Evaluation of Parameters Critical for Observing Nucleic Acids Inside LivingXenopus laevisOocytes by In-Cell NMR Spectroscopy

(2009) Robert Hänsel et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Fluorescein Redirects a Ruthenium−Octaarginine Conjugate to the Nucleus

(2009) Cindy A. Puckett et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Efficient gene silencing by delivery of locked nucleic acid antisense oligonucleotides, unassisted by transfection reagents

(2009) C. A. Stein et al.   NUCLEIC ACIDS RESEARCH

Time-resolved Microspectrofluorometry and Fluorescence Imaging Techniques: Study of Porphyrin-mediated Cellular Uptake of Oligonucleotides

(2008) Petr Praus et al.   Annals of the New York Academy of Sciences

Antisense inhibition of ICAM-1 expression as therapy provides insight into basic inflammatory pathways through early experiences in IBD

(2008) Jessica R Philpott et al.   EXPERT OPINION ON BIOLOGICAL THERAPY

Fluorescence correlation spectroscopy and fluorescence cross-correlation spectroscopy reveal the cytoplasmic origination of loaded nuclear RISC in vivo in human cells

(2008) Thomas Ohrt et al.   NUCLEIC ACIDS RESEARCH