1. Targeting RNA With Antisense Oligonucleotides and Small Interfering RNA in Dyslipidemias: JACC State-of-the-Art Review
- Author
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Katzmann, Julius, Packard, Chris, Chapman, M. John, Katzmann, Isabell, Laufs, Ulrich, University Hospital Leipzig, University of Glasgow, Service d’Endocrinologie, Métabolisme et Prévention des Risques Cardio-Vasculaires [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM), Zeisigwaldkliniken Bethanie Chemnits, Gestionnaire, HAL Sorbonne Université 5, Service d'Endocrinologie, Métabolisme et Prévention des Maladies Cardio-vasculaires [CHU Pitié-Salpêtrière], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
- Subjects
PCSK9 ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,angiopoietin-like 3? apolipoprotein CIII? ASO? lipoprotein(a) ,siRNA ,[SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system - Abstract
International audience; 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.
- Published
- 2020