Advances in siRNA therapeutics and synergistic effect on siRNA activity using emerging dual ribose modifications

Current Advances in RNA Therapeutics for Human Diseases

(2022) Hannah Zogg et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

The growth of siRNA-based therapeutics: updated clinical studies

(2021) M. May Zhang et al.   BIOCHEMICAL PHARMACOLOGY

Inclisiran: First Approval

(2021) Yvette N. Lamb   DRUGS

Synthesis, Structural, and Conformational Analysis of 4′‐ C ‐Alkyl‐2′‐ O ‐Ethyl‐Uridine Modified Nucleosides

(2021) Rahul R. Nikam et al.   EUROPEAN JOURNAL OF ORGANIC CHEMISTRY

Targeting of antithrombin in hemophilia A or B with investigational siRNA therapeutic fitusiran – results of the phase 1 inhibitor cohort

(2021) K. John Pasi et al.   JOURNAL OF THROMBOSIS AND HAEMOSTASIS

siRNAs containing 2′-fluorinated Northern-methanocarbacyclic (2′-F-NMC) nucleotides: in vitro and in vivo RNAi activity and inability of mitochondrial polymerases to incorporate 2′-F-NMC NTPs

(2021) Masaaki Akabane-Nakata et al.   NUCLEIC ACIDS RESEARCH

Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications

(2021) Christopher Liczner et al.   Beilstein Journal of Organic Chemistry

Delivery of oligonucleotide‐based therapeutics: challenges and opportunities

(2021) Suzan M Hammond et al.   EMBO Molecular Medicine

Lumasiran, an RNAi Therapeutic for Primary Hyperoxaluria Type 1

(2021) Sander F. Garrelfs et al.   NEW ENGLAND JOURNAL OF MEDICINE

Teprasiran, A Small Interfering RNA, for the Prevention of Acute Kidney Injury in High-Risk Patients Undergoing Cardiac Surgery: A Randomized Clinical Study

(2021) Matthias Thielmann et al.   CIRCULATION

siRNA: Mechanism of action, challenges, and therapeutic approaches

(2021) Walhan Alshaer et al.   EUROPEAN JOURNAL OF PHARMACOLOGY

Pharmacokinetics and Pharmacodynamics of the Small Interfering Ribonucleic Acid (siRNA), Givosiran, in Patients with Acute Hepatic Porphyria

(2020) Sagar Agarwal et al.   CLINICAL PHARMACOLOGY & THERAPEUTICS

Givosiran: First Approval

(2020) Lesley J. Scott   DRUGS

Chimeric siRNAs with chemically modified pentofuranose and hexopyranose nucleotides: altritol-nucleotide (ANA) containing GalNAc–siRNA conjugates: in vitro and in vivo RNAi activity and resistance to 5′-exonuclease

(2020) Pawan Kumar et al.   NUCLEIC ACIDS RESEARCH

Delivery of Oligonucleotides to the Liver with GalNAc: From Research to Registered Therapeutic Drug

(2020) Alexandre J. Debacker et al.   MOLECULAR THERAPY

Modified Nucleic Acids: Expanding the Capabilities of Functional Oligonucleotides

(2020) Steven Ochoa et al.   MOLECULES

Overcoming Barriers for siRNA Therapeutics: From Bench to Bedside

(2020) Muhammad Imran Sajid et al.   Pharmaceuticals

Synthesis and Biophysical Characterization of RNAs Containing 2′-Fluorinated Northern Methanocarbacyclic Nucleotides

(2019) Masaaki Akabane-Nakata et al.   ORGANIC LETTERS

The current state and future directions of RNAi-based therapeutics

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

Synthesis and Biophysical Characterization of RNAs Containing (R)- and (S)-5′-C-Aminopropyl-2′-O-methyluridines

(2019) Ryohei Kajino et al.   JOURNAL OF ORGANIC CHEMISTRY

siRNA therapeutics: a clinical reality

(2019) Phei Er Saw et al.   Science China-Life Sciences

Effect of Sugar 2′,4′-Modifications on Gene Silencing Activity of Small Interfering RNA Duplexes

(2019) Elise Malek-Adamian et al.   Nucleic Acid Therapeutics

Current Development of siRNA Bioconjugates: From Research to the Clinic

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

Synthesis and characterization of 4′-C-guanidinomethyl-2′-O-methyl-modified RNA oligomers

(2019) Azusa Uematsu et al.   NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS

The Onpattro story and the clinical translation of nanomedicines containing nucleic acid-based drugs

(2019) Akin Akinc et al.   Nature Nanotechnology

Synthesis of 4′- C -aminoalkyl-2′- O -methyl modified RNA and their biological properties

(2018) Kana Koizumi et al.   BIOORGANIC & MEDICINAL CHEMISTRY

RNA-Targeted Therapeutics

(2018) Stanley T. Crooke et al.   Cell Metabolism

Facile Synthesis, Geometry, and 2′-Substituent-Dependent in Vivo Activity of 5′-(E)- and 5′-(Z)-Vinylphosphonate-Modified siRNA Conjugates

(2018) Rubina Giare Parmar et al.   JOURNAL OF MEDICINAL CHEMISTRY

Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis

(2018) David Adams et al.   NEW ENGLAND JOURNAL OF MEDICINE

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

Selection of GalNAc-conjugated siRNAs with limited off-target-driven rat hepatotoxicity

(2018) Maja M. Janas et al.   Nature Communications

GalNAc-siRNA Conjugates: Leading the Way for Delivery of RNAi Therapeutics

(2018) Aaron D. Springer et al.   Nucleic Acid Therapeutics

Current Challenges in Delivery and Cytosolic Translocation of Therapeutic RNAs

(2018) Ludger Johannes et al.   Nucleic Acid Therapeutics

Synthesis and properties of 4′-C-aminoalkyl-2′-fluoro-modified RNA oligomers

(2018) Toshifumi Kano et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Patisiran: First Global Approval

(2018) Sheridan M. Hoy   DRUGS

Structural basis for the synergy of 4′- and 2′-modifications on siRNA nuclease resistance, thermal stability and RNAi activity

(2018) Joel M Harp et al.   NUCLEIC ACIDS RESEARCH

Chirality Dependent Potency Enhancement and Structural Impact of Glycol Nucleic Acid Modification on siRNA

(2017) Mark K. Schlegel et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

4′-C-Methoxy-2′-deoxy-2′-fluoro Modified Ribonucleotides Improve Metabolic Stability and Elicit Efficient RNAi-Mediated Gene Silencing

(2017) Elise Malek-Adamian et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Inclisiran in Patients at High Cardiovascular Risk with Elevated LDL Cholesterol

(2017) Kausik K. Ray et al.   NEW ENGLAND JOURNAL OF MEDICINE

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

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

The Race of 10 Synthetic RNAi-Based Drugs to the Pharmaceutical Market

(2017) Ricardo Titze-de-Almeida et al.   PHARMACEUTICAL RESEARCH

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

An Investigational RNAi Therapeutic Targeting Glycolate Oxidase Reduces Oxalate Production in Models of Primary Hyperoxaluria

(2016) Abigail Liebow et al.   JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY

siRNA carrying an (E)-vinylphosphonate moiety at the 5΄ end of the guide strand augments gene silencing by enhanced binding to human Argonaute-2

(2016) Elad Elkayam et al.   NUCLEIC ACIDS RESEARCH

Evolving landscape in the management of transthyretin amyloidosis

(2015) Philip N. Hawkins et al.   ANNALS OF MEDICINE

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

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

Synthesis and Duplex-Stabilizing Properties of FluorinatedN-Methanocarbathymidine Analogues Locked in the C3′-endoConformation

(2014) Michael E. Jung et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Chemistry, Properties, and in Vitro and in Vivo Applications of 2′-O-Methoxyethyl-4′-thioRNA, a Novel Hybrid Type of Chemically Modified RNA

(2014) Yota Saito et al.   CHEMBIOCHEM

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

Toxicological and Pharmacokinetic Properties of QPI-1007, a Chemically Modified Synthetic siRNA Targeting Caspase 2 mRNA, Following Intravitreal Injection

(2014) Elisabeth C.R. Solano et al.   Nucleic Acid Therapeutics

Phosphorothioates, Essential Components of Therapeutic Oligonucleotides

(2014) Fritz Eckstein   Nucleic Acid Therapeutics

Influence of 2′-Fluoro versus 2′-O-Methyl Substituent on the Sugar Puckering of 4′-C-Aminomethyluridine

(2013) Kiran R. Gore et al.   JOURNAL OF ORGANIC CHEMISTRY

Single-Stranded siRNAs Activate RNAi in Animals

(2012) Walt F. Lima et al.   CELL

Incorporation of 4′-C-aminomethyl-2′-O-methylthymidine into DNA by thermophilic DNA polymerases

(2012) Ganesh N. Nawale et al.   CHEMICAL COMMUNICATIONS

Designing Chemically Modified Oligonucleotides for Targeted Gene Silencing

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

Synthesis, Gene Silencing, and Molecular Modeling Studies of 4′-C-Aminomethyl-2′-O-methyl Modified Small Interfering RNAs

(2012) Kiran R. Gore et al.   JOURNAL OF ORGANIC CHEMISTRY

Intracellular stability of 2′-OMe-4′-thioribonucleoside modified siRNA leads to long-term RNAi effect

(2012) Mayumi Takahashi et al.   NUCLEIC ACIDS RESEARCH

Silencing disease genes in the laboratory and the clinic

(2011) Jonathan K Watts et al.   JOURNAL OF PATHOLOGY

Synthesis and Biophysical Evaluation of 2′,4′-Constrained 2′O-Methoxyethyl and 2′,4′-Constrained 2′O-Ethyl Nucleic Acid Analogues

(2010) Punit P. Seth et al.   JOURNAL OF ORGANIC CHEMISTRY

Utilization of unlocked nucleic acid (UNA) to enhance siRNA performance in vitro and in vivo

(2010) Maria B. Laursen et al.   Molecular BioSystems

Improved specificity of gene silencing by siRNAs containing unlocked nucleobase analogs

(2010) Narendra Vaish et al.   NUCLEIC ACIDS RESEARCH

UNA (unlocked nucleic acid): A flexible RNA mimic that allows engineering of nucleic acid duplex stability

(2009) Niels Langkjær et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Exploring Chemical Modifications for siRNA Therapeutics: A Structural and Functional Outlook

(2009) Siddharth Shukla et al.   ChemMedChem

Biological effects of hexitol and altritol-modified siRNAs targeting B-Raf

(2009) Michael Fisher et al.   EUROPEAN JOURNAL OF PHARMACOLOGY

Synthesis and characterization of 2′-modified-4′-thioRNA: a comprehensive comparison of nuclease stability

(2009) Mayumi Takahashi et al.   NUCLEIC ACIDS RESEARCH

Chemically modified siRNA: tools and applications

(2008) J WATTS et al.   DRUG DISCOVERY TODAY

Overcoming the Innate Immune Response to Small Interfering RNA

(2008) Adam Judge et al.   HUMAN GENE THERAPY

Chemical Modification of siRNAs for In Vivo Use

(2008) Mark A. Behlke   OLIGONUCLEOTIDES

The Argonaute protein family

(2008) Julia Höck et al.   GENOME BIOLOGY