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A Highly Durable RNAi Therapeutic Inhibitor of PCSK9

https://doi.org/10.1056/nejmoa1609243
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What this work says

Outgoing claims: the papers this work cites, builds on, or argues with.

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Biochemistry of Statins
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Results of Bococizumab, A Monoclonal Antibody Against Proprotein Convertase Subtilisin/Kexin Type 9, from a Randomized, Placebo-Controlled, Dose-Ranging Study in Statin-Treated Subjects With Hypercholesterolemia
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Improved outcome after acute coronary syndromes with an intensive versus standard lipid-lowering regimen: results from the Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis in Myocardial Infarction 22 (PROVE IT–TIMI 22) trial
inferredcites →https://doi.org/10.1016/j.atherosclerosis.2006.08.039openalex-snapshot
The C679X mutation in PCSK9 is present and lowers blood cholesterol in a Southern African population
inferredcites →https://doi.org/10.1016/j.ijcard.2014.06.049openalex-snapshot
Monotherapy with the PCSK9 inhibitor alirocumab versus ezetimibe in patients with hypercholesterolemia: Results of a 24week, double-blind, randomized Phase 3 trial
inferredcites →https://doi.org/10.1016/j.jacc.2012.08.986openalex-snapshot
Effects of AMG 145 on Low-Density Lipoprotein Cholesterol Levels
inferredcites →https://doi.org/10.1016/j.jacc.2013.11.002openalex-snapshot
2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults
inferredcites →https://doi.org/10.1016/j.jvs.2015.08.004openalex-snapshot
Efficacy and Safety of Evolocumab in Reducing Lipids and Cardiovascular Events
inferredcites →https://doi.org/10.1016/s0140-6736(12)61771-1openalex-snapshot
Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 as monotherapy in patients with hypercholesterolaemia (MENDEL): a randomised, double-blind, placebo-controlled, phase 2 study
inferredcites →https://doi.org/10.1016/s0140-6736(13)61914-5openalex-snapshot
Effect of an RNA interference drug on the synthesis of proprotein convertase subtilisin/kexin type 9 (PCSK9) and the concentration of serum LDL cholesterol in healthy volunteers: a randomised, single-blind, placebo-controlled, phase 1 trial
inferredcites →https://doi.org/10.1021/ja505986aopenalex-snapshot
Multivalent N -Acetylgalactosamine-Conjugated siRNA Localizes in Hepatocytes and Elicits Robust RNAi-Mediated Gene Silencing
inferredcites →https://doi.org/10.1056/nejmoa1105803openalex-snapshot
Effect of a Monoclonal Antibody to PCSK9 on LDL Cholesterol
inferredcites →https://doi.org/10.1056/nejmoa1208760openalex-snapshot
Safety and Efficacy of RNAi Therapy for Transthyretin Amyloidosis
inferredcites →https://doi.org/10.1056/nejmoa1500858openalex-snapshot
Efficacy and Safety of Evolocumab in Reducing Lipids and Cardiovascular Events
inferredcites →https://doi.org/10.1056/nejmoa1501031openalex-snapshot
Efficacy and Safety of Alirocumab in Reducing Lipids and Cardiovascular Events
inferredcites →https://doi.org/10.1073/pnas.0805434105openalex-snapshot
Therapeutic RNAi targeting PCSK9 acutely lowers plasma cholesterol in rodents and LDL cholesterol in nonhuman primates
inferredcites →https://doi.org/10.1086/507488openalex-snapshot
Molecular Characterization of Loss-of-Function Mutations in PCSK9 and Identification of a Compound Heterozygote
inferredcites →https://doi.org/10.1111/j.1365-2796.2009.02167.xopenalex-snapshot
The unique role of proprotein convertase subtilisin/kexin 9 in cholesterol homeostasis
inferredcites →https://doi.org/10.1124/jpet.114.221242openalex-snapshot
Anti-PCSK9 Antibody Pharmacokinetics and Low-Density Lipoprotein-Cholesterol Pharmacodynamics in Nonhuman Primates Are Antigen Affinity–Dependent and Exhibit Limited Sensitivity to Neonatal Fc Receptor–Binding Enhancement
inferredcites →https://doi.org/10.1158/2159-8290.cd-12-0429openalex-snapshot
First-in-Humans Trial of an RNA Interference Therapeutic Targeting VEGF and KSP in Cancer Patients with Liver Involvement
inferredcites →https://doi.org/10.1161/01.cir.0000437738.63853.7aopenalex-snapshot
2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults
inferredcites →https://doi.org/10.1161/jaha.112.001800openalex-snapshot
Prevalence of Dyslipidemia and Lipid Goal Attainment in Statin‐Treated Subjects From 3 Data Sources: A Retrospective Analysis
inferredcites →https://doi.org/10.1177/0003319714535073openalex-snapshot
Lipid Target Achievement Among Patients With Very High and High Cardiovascular Risk in a Lipid Clinic
inferredcites →https://doi.org/10.1185/03007995.2014.890926openalex-snapshot
Total and low-density lipoprotein cholesterol in high-risk patients treated with atorvastatin monotherapy in the United Kingdom: analysis of a primary-care database
inferredcites →https://doi.org/10.1186/s12916-015-0358-8openalex-snapshot
Safety and efficacy of anti-PCSK9 antibodies: a meta-analysis of 25 randomized, controlled trials
inferredcites →https://doi.org/10.1194/jlr.r800091-jlr200openalex-snapshot
PCSK9: a convertase that coordinates LDL catabolism
inferredcites →https://doi.org/10.1210/jc.2009-0141openalex-snapshot
Genetic and Metabolic Determinants of Plasma PCSK9 Levels
inferredcites →https://doi.org/10.1517/14712598.2012.748743openalex-snapshot
Anti-PCSK9 therapies for the treatment of hypercholesterolemia
inferredcites →https://doi.org/10.7326/m14-2957openalex-snapshot
Effects of Proprotein Convertase Subtilisin/Kexin Type 9 Antibodies in Adults With Hypercholesterolemia

What points at this work

Incoming claims: where this work appears in other papers’ reference lists and arguments.

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RNAi technique, how far is it from pediatrics?
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The N‐Acetylgalactosamine ‐conjugated small interfering RNA inclisiran can be coadministered safely with atorvastatin in cynomolgus monkeys resulting in additive low‐density lipoprotein cholesterol reductions
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RNA interference‐based exogenous double‐stranded RNAs confer resistance to Rhizoctonia solani AG ‐3 on Nicotiana tabacum
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A case‐study of model‐informed drug development of a novel PCSK9 anti sense oligonucleotide. Part 1: First time in man to phase II
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LDL-Cholesterol-Lowering Therapy
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Chemical Modifications in RNA Interference and CRISPR/Cas Genome Editing Reagents
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PCSK9 Inhibition and Atherosclerosis: Current Therapeutic Option and Prospection
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siRNA Design and GalNAc-Empowered Hepatic Targeted Delivery
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Delivery of Oligonucleotide Therapeutics for Macrophage Reprogramming in Inflammatory Diseases
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Emerging Lipoprotein-Related Therapeutics for Patients with Diabetes
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Atherosklerose-Risikofaktoren
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Lipids
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Gene Therapy in Pediatric Liver Disease
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Non-coding RNAs and Ischemic Cardiovascular Diseases
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Drug Discovery for Coronary Artery Disease
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PCSK9 Inhibiting Monoclonal Antibodies
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PCSK9 Inhibiting siRNA
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RNAi in the Postgenomic Era: Delivery, Drug Design, and Emerging Technologies
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Lipid nanoparticle-mediated siRNA delivery for safe targeting of human CML in vivo
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Physiological and therapeutic regulation of PCSK9 activity in cardiovascular disease
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Oxidized low-density lipoprotein (oxLDL) affects load-free cell shortening of cardiomyocytes in a proprotein convertase subtilisin/kexin 9 (PCSK9)-dependent way
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Regulation of angiogenesis by microRNAs in cardiovascular diseases
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Phase 3 Multicenter Study of Revusiran in Patients with Hereditary Transthyretin-Mediated (hATTR) Amyloidosis with Cardiomyopathy (ENDEAVOUR)
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Biotechnology Approaches for the Treatment of Dyslipidemia
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Correction to: Phase 3 Multicenter Study of Revusiran in Patients with Hereditary Transthyretin-Mediated (hATTR) Amyloidosis with Cardiomyopathy (ENDEAVOUR)
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Cholesterol Lowering Biotechnological Strategies: From Monoclonal Antibodies to Antisense Therapies. A Pre-Clinical Perspective Review
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Efficacy and Safety of Inclisiran in Patients with Polyvascular Disease: Pooled, Post Hoc Analysis of the ORION-9, ORION-10, and ORION-11 Phase 3 Randomized Controlled Trials
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Directing the Way—Receptor and Chemical Targeting Strategies for Nucleic Acid Delivery
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RNAi targeting LMAN1-MCFD2 complex promotes anticoagulation in mice
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PCSK9 targets important for lipid metabolism
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PCSK9 Mutations in Familial Hypercholesterolemia: from a Groundbreaking Discovery to Anti-PCSK9 Therapies
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Pleiotropic Anti-atherosclerotic Effects of PCSK9 Inhibitors From Molecular Biology to Clinical Translation
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New Pharmacological Approaches to Target PCSK9
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The Long Non-coding Road to Atherosclerosis
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The Role of RNA-Targeted Therapeutics to Reduce ASCVD Risk: What Have We Learned Recently?
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RNA Silencing in the Management of Dyslipidemias
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Major Concepts in Treatment with Bempedoic Acid and Inclisiran that Clinicians Need To Know
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Updates in Small Interfering RNA for the Treatment of Dyslipidemias
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The Role of Non-Statin Lipid Lowering Therapies to Reduce ASCVD Events in Primary Prevention
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Combination Lipid-Lowering Therapies for the Prevention of Recurrent Cardiovascular Events
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Is There a Need to Revise Goals in the Management of Dyslipidemias?
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Genetics, Dyslipidemia, and Cardiovascular Disease: New Insights
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Low-density Lipoprotein-Cholesterol Lowering Strategies for Prevention of Atherosclerotic Cardiovascular Disease: Focus on siRNA Treatment Targeting PCSK9 (Inclisiran)
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PCSK9 Inhibitor Wars: How Does Inclisiran Fit in with Current Monoclonal Antibody Inhibitor Therapy? Considerations for Patient Selection
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MicroRNAs: New Therapeutic Targets for Familial Hypercholesterolemia?
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Emerging Lipid-Lowering Therapies in Secondary Prevention
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The Role of Extracellular Non-coding RNAs in Atherosclerosis
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Working towards full eradication of lipid-driven cardiovascular risk?
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inferred← citeshttps://doi.org/10.1007/s15027-016-1020-xopenalex-snapshot
Starke LDL-Senkung mit nur einer Injektion?
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Current drugs, targets, and drug delivery systems for the treatment of dyslipidemia
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Comparative Effectiveness of Inclisiran 100, 300, and 500 mg in a Population with Hyperlipidemia: A Network Meta-Analysis of Randomized Controlled Trials
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A Meta-analysis of the Regulation of Low-Density Lipoprotein Cholesterol and Proprotein Convertase Subtilisin-Kexin Type 9 with Inclisiran
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inferred← citeshttps://doi.org/10.1007/s40259-017-0220-yopenalex-snapshot
PCSK9 Inhibitors in Hyperlipidemia: Current Status and Clinical Outlook
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Small Interfering RNA Therapeutic Inclisiran: A New Approach to Targeting PCSK9
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Therapeutic siRNA: State-of-the-Art and Future Perspectives
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Lipid Management in Chronic Kidney Disease: Systematic Review of PCSK9 Targeting
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Outcomes, Access, and Cost Issues Involving PCSK9 Inhibitors to Lower LDL-Cholesterol
inferred← citeshttps://doi.org/10.1007/s40265-021-01473-6openalex-snapshot
Inclisiran: First Approval
inferred← citeshttps://doi.org/10.1007/s40265-025-02173-1openalex-snapshot
The Potential of RNA Therapeutics in Treating Cardiovascular Disease
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Are PCSK9 Inhibitors Cost Effective?
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Low Density Lipoprotein (LDL) Cholesterol as a Causal Role for Atherosclerotic Disease: Potential Role of PCSK9 Inhibitors
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Reduction of High Cholesterol Levels by a Preferably Fixed-Combination Strategy as the First Step in the Treatment of Hypertensive Patients with Hypercholesterolemia and High/Very High Cardiovascular Risk: A Consensus Document by the Italian Society of Hypertension
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Cyclosporin A-Induced Dyslipidemia and LDL Receptors
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Controlling Protein Expression by Delivery of RNA Therapeutics Using Lipid Nanoparticles
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RNA therapies for cardiovascular disease
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Principles of novel cellular and molecular cardiovascular therapeutics
inferred← citeshttps://doi.org/10.1016/b978-0-323-85857-1.00033-xopenalex-snapshot
Familial hypercholesterolemia
inferred← citeshttps://doi.org/10.1016/b978-0-323-85857-1.00036-5openalex-snapshot
Cholesterol and alcohol
inferred← citeshttps://doi.org/10.1016/b978-0-323-88286-6.00021-2openalex-snapshot
Inclisiran
inferred← citeshttps://doi.org/10.1016/b978-0-323-99991-5.00009-7openalex-snapshot
Proprotein convertase subtilisin kexin type 9 inhibitors and other novel lipid-modifying drugs: broadening the perspective of cardiovascular disease prevention
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Recent advances in siRNA delivery mediated by lipid-based nanoparticles
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Non-viral nanoparticles for RNA interference: Principles of design and practical guidelines
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Modulating intracellular pathways to improve non-viral delivery of RNA therapeutics
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Design of VICTORION-2 Prevent: A randomized double-blind, placebo-controlled trial, assessing the impact of inclisiran on major adverse cardiovascular events in patients with established cardiovascular disease
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HPS-4/TIMI 65/ORION-4: A double-blind randomized placebo-controlled trial assessing the effects of inclisiran on clinical outcomes among people with atherosclerotic cardiovascular disease: Trial design, recruitment, and baseline characteristics
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Efficacy and safety of inclisiran a newly approved FDA drug: a systematic review and pooled analysis of available clinical studies
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Effectiveness and Safety of Inclisiran, A Novel Long-Acting RNA Therapeutic Inhibitor of Proprotein Convertase Subtilisin/Kexin 9
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A Meta-Analysis of Cardiovascular Outcomes in Patients With Hypercholesterolemia Treated With Inclisiran
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Meta-Analysis of Inclisiran for the Treatment of Hypercholesterolemia
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Familial Hypercholesterolemia Among Young Adults With Acute Coronary Syndrome
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The Impact of Inclisiran on Lipid Profiles in Adults with Hyperlipidemia: A Meta-Analysis and Meta-Regression of Randomized Controlled Trials
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Novel and Emerging Therapeutics for Primary Prevention of Cardiovascular Disease
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The Role of Lipoprotein(a) in the Progression of Aortic Stenosis
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Development of a highly stable, active small interfering RNA with broad activity against SARS-CoV viruses
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Design, synthesis, and biological evaluation of novel tetrahydroprotoberberine derivatives (THPBs) as proprotein convertase subtilisin/kexin type 9 (PCSK9) modulators for the treatment of hyperlipidemia
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Lipid-nanoparticle-enabled nucleic acid therapeutics for liver disorders
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New and Future Parenteral Therapies for the Management of Lipid Disorders
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Efficacy, benefit and safety of inclisiran
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Eficacia, beneficio y seguridad de inclisiran
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Familial hypercholesterolemia treatments: Guidelines and new therapies
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Endocytosis of lipoproteins
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2019 ESC/EAS guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk
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PCSK9-D374Y mediated LDL-R degradation can be functionally inhibited by EGF-A and truncated EGF-A peptides: An in vitro study
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Estimation of the major cardiovascular events prevention with Inclisiran
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Consensus clinical recommendations for the management of plasma lipid disorders in the Middle East: 2021 update
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The emerging role of glycans and the importance of sialylation in cardiovascular disease
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The evolving therapeutic landscape of PCSK9 inhibition
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Executive summary of the Hellenic Atherosclerosis Society guidelines for the diagnosis and treatment of dyslipidemias - 2023
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Emerging oral therapeutic strategies for inhibiting PCSK9
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Effect of modification of siRNA molecules delivered with aminopropylsilanol nanoparticles on suppression of A/H5N1 virus in cell culture
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Preferential cleavage of upstream targets in concatenated miRNA/siRNA target sites support a 5′-3′ scanning model for RISC target recognition
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Keep recycling going: New approaches to reduce LDL-C
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The growth of siRNA-based therapeutics: Updated clinical studies
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Robust loading and delivery of functional small RNAs via protein N-myristoylation-induced small extracellular vesicles
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Role of PCSK9 in lipid metabolism and atherosclerosis
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Inclisiran in lipid management: A Literature overview and future perspectives
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Therapeutic oligonucleotide ASC1R shows excellent tolerability and remarkable efficacy in reducing SARS-CoV-2 mRNA levels in C57BL/6 mice
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Binding domains of α-synuclein receptors with monomeric/oligomeric α-synuclein: Implications for Parkinson’s disease
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RNAi therapeutic and its innovative biotechnological evolution
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Introduction of 2-O-benzyl abasic nucleosides to the 3′-overhang regions of siRNAs greatly improves nuclease resistance
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Molecular glycoengineering of carbohydrate-functionalized nanocarriers for receptor-mediated targeted drug delivery in cancer
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Late-breaking Trials from the 2016 American Heart Association's Scientific Sessions
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Proprotein Convertase Subtilisin Kexin 9 Inhibitors
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10.1016/j.ccol.2023.02.007
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Systemic Factors in Temporomandibular Disorder Pain
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Progress of research on dyslipidemia accompanied by nephrotic syndrome
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Beyond Statins: New Therapeutic Frontiers for Cardiovascular Disease
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Safe and effective in vivo delivery of DNA and RNA using proteolipid vehicles
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Clearance of plasma PCSK9 via the asialoglycoprotein receptor mediated by heterobifunctional ligands
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Targeting RNA with synthetic oligonucleotides: Clinical success invites new challenges
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Lipid Metabolism and Emerging Targets for Lipid-Lowering Therapy
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The Promise of PCSK9 and Lipoprotein(a) as Targets for Gene Silencing Therapies
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RNA-Targeted Therapeutics
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A Pharmacologic Update
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Inclisiran siRNA technology in the management of dyslipidemia: A narrative review of clinical trials
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PCSK9 in the liver metastatic niche: From cholesterol homeostasis to tumor microenvironment reprogramming
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Drug metabolism and pharmacokinetic strategies for oligonucleotide- and mRNA-based drug development
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Harnessing nucleic acid-based therapeutics for atherosclerotic cardiovascular disease: state of the art
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Target discovery using biobanks and human genetics
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Opportunities and challenges of physiologically based pharmacokinetic modeling in drug delivery
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New and Emerging Therapies for Dyslipidemia
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One year after the ESC/EAS guidelines on cholesterol control. What's the new evidence? What's missing?
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Lipid lowering agents of natural origin: An account of some promising chemotypes
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Small molecules as inhibitors of PCSK9: Current status and future challenges
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From methylene bridged diindole to carbonyl linked benzimidazoleindole: Development of potent and metabolically stable PCSK9 modulators
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Recent trends in the delivery of RNA drugs: Beyond the liver, more than vaccine
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siRNA: Mechanism of action, challenges, and therapeutic approaches
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The evolving landscape of PCSK9 inhibition in cancer
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siRNA as potential therapeutic strategy for hypertension
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Innovative hypertension treatments: Transitioning from conventional therapies to siRNA-based solutions
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Tetrahydroberberrubine improves hyperlipidemia by activating the AMPK/SREBP2/PCSK9/LDL receptor signaling pathway
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American Association of Clinical Endocrinology Clinical Practice Guideline on Pharmacologic Management of Adults With Dyslipidemia
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Metabolismo del colesterol y mecanismos de acción de los fármacos hipolipemiantes
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Cell and gene therapeutic approaches in non-alcoholic fatty liver disease
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Ex vivo machine perfusion enables robust and widespread lipophilic-conjugated siRNA delivery to the porcine lung
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New Frontiers in the Treatment of Homozygous Familial Hypercholesterolemia
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Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor Eligibility and Prescription Rates in Patients Presenting With Recurrent Acute Coronary Syndromes
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Emerging role of sphingolipids and extracellular vesicles in development and therapeutics of cardiovascular diseases
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Selective modulator of nuclear receptor PPARγ with reduced adipogenic potential ameliorates experimental nephrotic syndrome
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Advances in Cardiovascular Care
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Cardiovascular Precision Medicine in the Genomics Era
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Inhibition of Factor XI Using RBD4059
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Small Interfering RNA Therapy Targeting the Long Noncoding RNA SMILR for Therapeutic Intervention in Coronary Artery Bypass Graft Failure
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