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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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Updated: Jun 25, 2025

An Adipocyte Cell Culture Model to Study the Impact of Protein and Micro-RNA Modulation on Adipocyte Function
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Plozasiran, an RNA Interference Agent Targeting APOC3, for Mixed Hyperlipidemia.

Christie M Ballantyne1, Szilard Vasas1, Masoud Azizad1

  • 1From the Baylor College of Medicine and the Texas Heart Institute, Houston (C.M.B.); Borbánya Praxis, Nyíregyháza, Hungary (S.V.); Valley Clinical Trials, Northridge (M.A.), Arrowhead Pharmaceuticals, Pasadena (T.C., S.M., R.Z., M.M., J.H.), and the Stanford School of Medicine, Stanford (N.J.L.) - all in California; the Royal Adelaide Hospital, Adelaide, SA, Australia (P.C.); the Icahn School of Medicine at Mount Sinai, New York (R.S.R.); and the Department of Medicine, Université de Montréal and Ecogene-21, Quebec, QC, Canada (D.G.).

The New England Journal of Medicine
|May 28, 2024
PubMed
Summary
This summary is machine-generated.

Plozasiran significantly reduced triglyceride levels in patients with mixed hyperlipidemia. This hepatocyte-targeted therapy shows promise for managing atherosclerotic cardiovascular disease risk.

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Area of Science:

  • Cardiovascular Medicine
  • Pharmacology
  • Genetics

Background:

  • Mixed hyperlipidemia elevates atherosclerotic cardiovascular disease risk due to high non-high-density lipoprotein (HDL) cholesterol.
  • Triglyceride-rich lipoprotein metabolism is regulated by apolipoprotein C3 (APOC3), which inhibits lipoprotein lipase.

Purpose of the Study:

  • To evaluate the safety and efficacy of plozasiran, an APOC3-targeting small interfering RNA, in patients with mixed hyperlipidemia.
  • To assess the impact of plozasiran on fasting triglyceride levels over 48 weeks.

Main Methods:

  • A 48-week, phase 2b, double-blind, randomized, placebo-controlled trial was conducted.
  • Participants received subcutaneous plozasiran (10-50 mg) or placebo quarterly or half-yearly.
  • The primary endpoint was the percent change in fasting triglyceride level at 24 weeks.

Main Results:

  • Plozasiran demonstrated significant reductions in fasting triglyceride levels at 24 weeks across all tested doses and regimens compared to placebo.
  • Reductions ranged from -44.2 to -62.4 percentage points (P<0.001).
  • Worsening glycemic control was observed in 7-21% of plozasiran recipients versus 10% of placebo recipients.

Conclusions:

  • Plozasiran significantly reduced triglyceride levels in patients with mixed hyperlipidemia.
  • Further clinical outcomes trials are warranted to confirm the long-term efficacy and safety of plozasiran.