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Cited by 99Lipoproteins and Cardiovascular HealthRNA Interference and Gene DeliveryLipid metabolism and disorders

Targeting RNA With Antisense Oligonucleotides and Small Interfering RNA in Dyslipidemias

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Katzmann, Julius L., Packard, Chris J., Chapman, M. John, Katzmann, Isabell, Laufs, Ulrich·2020·Journal of the American College of Cardiology
DOI 10.1016/j.jacc.2020.05.070
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Abstract

There is an unmet clinical need to reduce residual cardiovascular risk attributable to apolipoprotein B-containing lipoproteins, particularly low-density lipoprotein and remnant particles. Pharmacological targeting of messenger RNA represents an emerging, innovative approach. Two major classes of agents have been developed-antisense oligonucleotides and small interfering RNA. Early problems with their use have been overcome by conjugation with N-acetylgalactosamine, an adduct that targets their delivery to the primary site of action in the liver. Using these agents to inhibit the translation of key regulatory proteins such as PCSK9, apolipoprotein CIII, apolipoprotein(a), and angiopoietin-like 3 has been shown to be effective in attenuating dyslipidemic states. Cardiovascular outcome trials with N-acetylgalactosamine-conjugated RNA-targeting drugs are ongoing. The advantages of these agents include long dosing intervals of up to 6 months and the potential to regulate the abundance of any disease-related protein. Long-term safety has yet to be demonstrated in large-scale clinical trials.

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Cited by

Sorted by citations

Authors
Katzmann, J. L., Packard, C. J., Chapman, M. J., Katzmann, I., & Laufs, U.
Affiliations
  • University Hospital Leipzig (DE)
  • University of Glasgow (GB)
  • Inserm (FR)
Corresponding author
Katzmann, Julius L.
ORCID
Venue
Journal of the American College of Cardiology
Publisher
Elsevier BV
Published
2020-08
Volume
76
Issue
5
Pages
563-579
ISSN
0735-1097 (ISSN-L)
DOI
10.1016/j.jacc.2020.05.070
OpenAlex
W3044543495
Cited by
99
References
27
Citations by year
2026: 17 · 2025: 18 · 2024: 13 · 2023: 15 · 2022: 21 · 2021: 11 · 2020: 4
FWCI
2.88
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of the American College of Cardiology (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
Funders
  • Amgen
  • Merck KGaA
  • Commonwealth Serum Laboratories
  • Sanofi
  • Pfizer
  • Kowa Company
Topics
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
Keywords
antisense oligonucleotides, siRNA, RNA-targeting drugs, dyslipidemia, PCSK9 inhibition, apolipoprotein C-III, apolipoprotein(a), ANGPTL3, low-density lipoprotein, remnant lipoproteins, cardiovascular risk reduction, liver-targeted drug delivery, cardiovascular outcome trials, drug safety
MeSH terms
Hypolipidemic Agents, Humans, Oligonucleotides, Antisense, RNA, Small Interfering, Dyslipidemias

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