Pharmacokinetics and Clinical Pharmacology Considerations of GalNAc3-Conjugated Antisense Oligonucleotides

Treating Disease at the RNA Level with Oligonucleotides

(2019) Arthur A. Levin   NEW ENGLAND JOURNAL OF MEDICINE

INHIBITION OF APOLIPOPROTEIN C-III WITH GALNAC CONJUGATED ANTISENSE DRUG POTENTLY LOWERS FASTING SERUM APOLIPOPROTEIN C-III AND TRIGLYCERIDE LEVELS IN HEALTHY VOLUNTEERS WITH ELEVATED TRIGLYCERIDES

(2018) Veronica J. Alexander et al.   JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

Evaluation of GalNAc-siRNA Conjugate Activity in Pre-clinical Animal Models with Reduced Asialoglycoprotein Receptor Expression

(2018) Jennifer L.S. Willoughby et al.   MOLECULAR THERAPY

The expanding role of prodrugs in contemporary drug design and development

(2018) Jarkko Rautio et al.   NATURE REVIEWS DRUG DISCOVERY

Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis

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

Inotersen Treatment for Patients with Hereditary Transthyretin Amyloidosis

(2018) Merrill D. Benson et al.   NEW ENGLAND JOURNAL OF MEDICINE

Nusinersen versus Sham Control in Later-Onset Spinal Muscular Atrophy

(2018) Eugenio Mercuri et al.   NEW ENGLAND JOURNAL OF MEDICINE

The Effects of 2′-O-Methoxyethyl Oligonucleotides on Renal Function in Humans

(2018) Stanley T. Crooke et al.   Nucleic Acid Therapeutics

Receptor-Mediated Uptake of Phosphorothioate Antisense Oligonucleotides in Different Cell Types of the Liver

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

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

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

Integrated Assessment of the Clinical Performance of GalNAc3-Conjugated 2′-O-Methoxyethyl Chimeric Antisense Oligonucleotides: I. Human Volunteer Experience

(2018) Stanley T. Crooke et al.   Nucleic Acid Therapeutics

The APPROACH Study: A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of Volanesorsen Administered Subcutaneously to Patients with Familial Chylomicronemia Syndrome (FCS)

(2017) D. Gaudet et al.   Journal of Clinical Lipidology

Population Pharmacokinetics of Nusinersen in the Cerebral Spinal Fluid and Plasma of Pediatric Patients With Spinal Muscular Atrophy Following Intrathecal Administrations

(2017) Kenneth T. Luu et al.   JOURNAL OF CLINICAL PHARMACOLOGY

Scientific white paper on concentration-QTc modeling

(2017) Christine Garnett et al.   JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS

Cardiovascular and Metabolic Effects of ANGPTL3 Antisense Oligonucleotides

(2017) Mark J. Graham et al.   NEW ENGLAND JOURNAL OF MEDICINE

Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy

(2017) Richard S. Finkel et al.   NEW ENGLAND JOURNAL OF MEDICINE

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

Eteplirsen in the treatment of Duchenne muscular dystrophy

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

Lack of QT Prolongation for 2′-O-Methoxyethyl-Modified Antisense Oligonucleotides Based on Retrospective Exposure/Response Analysis of Ten Phase 1 Dose-Escalation Placebo-Controlled Studies in Healthy Subjects

(2017) Rosie Z. Yu et al.   Nucleic Acid Therapeutics

Co-Administration of an Excipient Oligonucleotide Helps Delineate Pathways of Productive and Nonproductive Uptake of Phosphorothioate Antisense Oligonucleotides in the Liver

(2017) Aaron J. Donner et al.   Nucleic Acid Therapeutics

The Effects of 2′-O-Methoxyethyl Containing Antisense Oligonucleotides on Platelets in Human Clinical Trials

(2017) Stanley T. Crooke et al.   Nucleic Acid Therapeutics

Assessment of the Drug Interaction Potential of Unconjugated and GalNAc 3 -Conjugated 2′-MOE-ASOs

(2017) Colby S. Shemesh et al.   Molecular Therapy-Nucleic Acids

Preclinical and Clinical Advances of GalNAc-Decorated Nucleic Acid Therapeutics

(2017) Yuanyu Huang   Molecular Therapy-Nucleic Acids

Conjugation of mono and di-GalNAc sugars enhances the potency of antisense oligonucleotides via ASGR mediated delivery to hepatocytes

(2016) Garth A. Kinberger et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Alcoholic vs non-alcoholic fatty liver in rats: distinct differences in endocytosis and vesicle trafficking despite similar pathology

(2016) Karuna Rasineni et al.   BMC GASTROENTEROLOGY

Long-term mipomersen treatment is associated with a reduction in cardiovascular events in patients with familial hypercholesterolemia

(2016) P. Barton Duell et al.   Journal of Clinical Lipidology

Development of antibody-siRNA conjugate targeted to cardiac and skeletal muscles

(2016) Tsukasa Sugo et al.   JOURNAL OF CONTROLLED RELEASE

Exosomes as therapeutics: The implications of molecular composition and exosomal heterogeneity

(2016) Scott W. Ferguson et al.   JOURNAL OF CONTROLLED RELEASE

Antisense oligonucleotides targeting apolipoprotein(a) in people with raised lipoprotein(a): two randomised, double-blind, placebo-controlled, dose-ranging trials

(2016) Nicholas J Viney et al.   LANCET

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

Lack of Interactions Between an Antisense Oligonucleotide with 2′-O-(2-Methoxyethyl) Modifications and Major Drug Transporters

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

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

Elucidation of the Biotransformation Pathways of a Galnac3-conjugated Antisense Oligonucleotide in Rats and Monkeys

(2016) Colby S Shemesh et al.   Molecular Therapy-Nucleic Acids

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

Efficient Synthesis and Biological Evaluation of 5′-GalNAc Conjugated Antisense Oligonucleotides

(2015) Michael E. Østergaard et al.   BIOCONJUGATE CHEMISTRY

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

No effect on QT intervals of mipomersen, a 2′-O-methoxyethyl modified antisense oligonucleotide targeting ApoB-100 mRNA, in a phase I dose escalation placebo-controlled study, and confirmed by a thorough QT (tQT) study, in healthy subjects

(2015) Rosie Z. Yu et al.   EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY

Variable asialoglycoprotein receptor 1 expression in liver disease: Implications for therapeutic intervention

(2015) Dominik Witzigmann et al.   HEPATOLOGY RESEARCH

Asialoglycoprotein receptor mediated hepatocyte targeting — Strategies and applications

(2015) Anisha A. D'Souza et al.   JOURNAL OF CONTROLLED RELEASE

Antisense therapy targeting apolipoprotein(a): a randomised, double-blind, placebo-controlled phase 1 study

(2015) Sotirios Tsimikas et al.   LANCET

Exosome-delivered microRNAs modulate the inflammatory response to endotoxin

(2015) Margaret Alexander et al.   Nature Communications

Predictive Dose-Based Estimation of Systemic Exposure Multiples in Mouse and Monkey Relative to Human for Antisense Oligonucleotides With 2′-O-(2-Methoxyethyl) Modifications

(2015) Rosie Z Yu et al.   Molecular Therapy-Nucleic Acids

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

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

Physiological Roles of Asialoglycoprotein Receptors (ASGPRs) Variants and Recent Advances in Hepatic-Targeted Delivery of Therapeutic Molecules Via ASGPRs

(2014) Jing Hu et al.   PROTEIN AND PEPTIDE LETTERS

Clinical pharmacokinetics of second generation antisense oligonucleotides

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

Prodrugs--from Serendipity to Rational Design

(2011) K. M. Huttunen et al.   PHARMACOLOGICAL REVIEWS

Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells

(2011) María Mittelbrunn et al.   Nature Communications

A New Splice Variant of the Major Subunit of Human Asialoglycoprotein Receptor Encodes a Secreted Form in Hepatocytes

(2010) Jia Liu et al.   PLoS One

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

Autoantibodies to asialoglycoprotein receptor (ASGPR) measured by a novel ELISA—Revival of a disease-activity marker in autoimmune hepatitis

(2009) Gert Hausdorf et al.   CLINICA CHIMICA ACTA

Antisense oligonucleotide pharmacokinetics and metabolism

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

Prodrugs: design and clinical applications

(2008) Jarkko Rautio et al.   NATURE REVIEWS DRUG DISCOVERY