Antisense Oligonucleotides and Small Interfering RNA for the Treatment of Dyslipidemias
The burden of atherosclerotic disease worldwide necessitates implementing the treatment of its risk factors. Among them, hypercholesterolemia has a central role. In addition to conventional small organic compounds and the recently introduced monoclonal antibodies, new technologies are arising such a...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-07-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/11/13/3884 |
| _version_ | 1797408795123515392 |
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| author | Clarice Gareri Alberto Polimeni Salvatore Giordano Laura Tammè Antonio Curcio Ciro Indolfi |
| author_facet | Clarice Gareri Alberto Polimeni Salvatore Giordano Laura Tammè Antonio Curcio Ciro Indolfi |
| author_sort | Clarice Gareri |
| collection | DOAJ |
| description | The burden of atherosclerotic disease worldwide necessitates implementing the treatment of its risk factors. Among them, hypercholesterolemia has a central role. In addition to conventional small organic compounds and the recently introduced monoclonal antibodies, new technologies are arising such as the antisense oligonucleotides and small interfering RNAs (siRNAs) that operate upstream, blocking the mRNA translation of the proteins specifically involved in lipid metabolism. In this review, we briefly explain the mechanisms of action of these molecules and discuss the difficulties related to their in vivo use as therapeutical agents. We go over the oligonucleotides tested in clinical trials that could potentially revolutionize the care of patients by acting on proteins involved in the lipoprotein metabolism and regulation, namely: angiopoietin-like protein 3 (ANGPTL3); lipoprotein a (Lp(a)); apolipoprotein B (Apo B); apolipoprotein C III (Apo C-III); and proprotein convertase subtilisin–kexin type 9 (PCSK9). Finally, the differences between ASOs and siRNAs, their future possible clinical applications, and the role of Inclisiran, a siRNA direct against PCSK9 to reduce LDL-C, were reviewed in detail. |
| first_indexed | 2024-03-09T04:04:43Z |
| format | Article |
| id | doaj.art-917ec101a0294194bc7cd116e2686898 |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-09T04:04:43Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-917ec101a0294194bc7cd116e26868982023-12-03T14:09:06ZengMDPI AGJournal of Clinical Medicine2077-03832022-07-011113388410.3390/jcm11133884Antisense Oligonucleotides and Small Interfering RNA for the Treatment of DyslipidemiasClarice Gareri0Alberto Polimeni1Salvatore Giordano2Laura Tammè3Antonio Curcio4Ciro Indolfi5Division of Cardiology, Department of Medical and Surgical Sciences, Magna Graecia University, 88100 Catanzaro, ItalyDivision of Cardiology, Department of Medical and Surgical Sciences, Magna Graecia University, 88100 Catanzaro, ItalyDivision of Cardiology, Department of Medical and Surgical Sciences, Magna Graecia University, 88100 Catanzaro, ItalyDivision of Cardiology, Department of Medical and Surgical Sciences, Magna Graecia University, 88100 Catanzaro, ItalyDivision of Cardiology, Department of Medical and Surgical Sciences, Magna Graecia University, 88100 Catanzaro, ItalyDivision of Cardiology, Department of Medical and Surgical Sciences, Magna Graecia University, 88100 Catanzaro, ItalyThe burden of atherosclerotic disease worldwide necessitates implementing the treatment of its risk factors. Among them, hypercholesterolemia has a central role. In addition to conventional small organic compounds and the recently introduced monoclonal antibodies, new technologies are arising such as the antisense oligonucleotides and small interfering RNAs (siRNAs) that operate upstream, blocking the mRNA translation of the proteins specifically involved in lipid metabolism. In this review, we briefly explain the mechanisms of action of these molecules and discuss the difficulties related to their in vivo use as therapeutical agents. We go over the oligonucleotides tested in clinical trials that could potentially revolutionize the care of patients by acting on proteins involved in the lipoprotein metabolism and regulation, namely: angiopoietin-like protein 3 (ANGPTL3); lipoprotein a (Lp(a)); apolipoprotein B (Apo B); apolipoprotein C III (Apo C-III); and proprotein convertase subtilisin–kexin type 9 (PCSK9). Finally, the differences between ASOs and siRNAs, their future possible clinical applications, and the role of Inclisiran, a siRNA direct against PCSK9 to reduce LDL-C, were reviewed in detail.https://www.mdpi.com/2077-0383/11/13/3884hypercholesterolemiamiRNAASOsiRNAF |
| spellingShingle | Clarice Gareri Alberto Polimeni Salvatore Giordano Laura Tammè Antonio Curcio Ciro Indolfi Antisense Oligonucleotides and Small Interfering RNA for the Treatment of Dyslipidemias Journal of Clinical Medicine hypercholesterolemia miRNA ASO siRNAF |
| title | Antisense Oligonucleotides and Small Interfering RNA for the Treatment of Dyslipidemias |
| title_full | Antisense Oligonucleotides and Small Interfering RNA for the Treatment of Dyslipidemias |
| title_fullStr | Antisense Oligonucleotides and Small Interfering RNA for the Treatment of Dyslipidemias |
| title_full_unstemmed | Antisense Oligonucleotides and Small Interfering RNA for the Treatment of Dyslipidemias |
| title_short | Antisense Oligonucleotides and Small Interfering RNA for the Treatment of Dyslipidemias |
| title_sort | antisense oligonucleotides and small interfering rna for the treatment of dyslipidemias |
| topic | hypercholesterolemia miRNA ASO siRNAF |
| url | https://www.mdpi.com/2077-0383/11/13/3884 |
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