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Related Concept Videos

siRNA - Small Interfering RNAs02:30

siRNA - Small Interfering RNAs

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Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
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Lipid-Lowering Drugs: Statins and Miscellaneous Agents01:20

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Hyperlipidemia, a medical condition often referred to as high cholesterol, is characterized by abnormally elevated levels of lipids in the bloodstream. When present in excess, these lipids, specifically cholesterol and triglycerides, can lead to serious health complications, often involving cardiovascular diseases. Illnesses like atherosclerosis, heart attacks, and pancreatitis have all been linked to untreated hyperlipidemia. This means controlling and regulating cholesterol and triglyceride...
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Experimental RNAi02:15

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RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
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Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...
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Related Experiment Video

Updated: Sep 6, 2025

Long-term Silencing of Intersectin-1s in Mouse Lungs by Repeated Delivery of a Specific siRNA via Cationic Liposomes. Evaluation of Knockdown Effects by Electron Microscopy
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Long-term Silencing of Intersectin-1s in Mouse Lungs by Repeated Delivery of a Specific siRNA via Cationic Liposomes. Evaluation of Knockdown Effects by Electron Microscopy

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Inclisiran: A First-in-Class siRNA Therapy for Lowering Low-Density Lipoprotein Cholesterol.

Essie Samuel1, Maya Watford1, Ugochukwu O Egolum2

  • 1Department of Pharmacy Practice, School of Pharmacy, Philadelphia College of Osteopathic Medicine, Suwanee, GA, USA.

The Annals of Pharmacotherapy
|July 1, 2022
PubMed
Summary
This summary is machine-generated.

Inclisiran effectively lowers low-density lipoprotein cholesterol (LDL-C) through a novel RNA interference mechanism. Further research is needed to confirm its long-term safety and impact on cardiovascular outcomes.

Keywords:
cholesterolinclisiransiRNA therapy

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Area of Science:

  • Cardiovascular Pharmacology
  • RNA Interference Therapeutics
  • Lipid Metabolism

Background:

  • Inclisiran represents a novel therapeutic approach for managing dyslipidemia.
  • It targets the proprotein convertase subtilisin/kexin type 9 (PCSK9) pathway.
  • Understanding its profile is crucial for clinical application.

Purpose of the Study:

  • To comprehensively review the pharmacology, pharmacokinetics/pharmacodynamics, safety, and efficacy of inclisiran.
  • To assess its role in lowering low-density lipoprotein cholesterol (LDL-C).
  • To identify gaps in current knowledge regarding clinical outcomes and long-term safety.

Main Methods:

  • Systematic literature search of PubMed and ClinicalTrials.gov (December 2014–April 2022).
  • Inclusion of English-language studies evaluating inclisiran in humans.
  • Hand-searching of references for additional relevant articles.

Main Results:

  • Inclisiran is a small interfering RNA (siRNA) therapy administered subcutaneously twice yearly.
  • It inhibits PCSK9 synthesis, increasing LDL receptor expression and reducing LDL-C levels.
  • Phase II/III trials show comparable LDL-C reduction to PCSK9 inhibitors, with similar safety profiles except for injection-site reactions.

Conclusions:

  • Inclisiran demonstrates efficacy and safety in lowering LDL-C.
  • It may benefit patients with atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia.
  • Further data on clinical outcomes and long-term safety are required.