Loading...
Synthesis of Novel MicroRNA-30c Analogs to Reduce Apolipoprotein B Secretion in Human Hepatoma Cells.
Journal Title
Bio-protocol
Readers/Advisors
Journal Title
Term and Year
Publication Date
2022-12-20
Book Title
Publication Volume
12
Publication Issue
24
Publication Begin
Publication End
Number of pages
Collections
Files
Loading...
Bio-protocol4574.pdf
Adobe PDF, 1.05 MB
Research Projects
Organizational Units
Journal Issue
Abstract
Atherosclerosis, a condition characterized by thickening of the arteries due to lipid deposition, is the major contributor to and hallmark of cardiovascular disease. Although great progress has been made in lowering the lipid plaques in patients, the conventional therapies fail to address the needs of those that are intolerant or non-responsive to the treatment. Therefore, additional novel therapeutic approaches are warranted. We have previously shown that increasing the cellular amounts of microRNA-30c (miR-30c) with the aid of viral vectors or liposomes can successfully reduce plasma cholesterol and atherosclerosis in mice. To avoid the use of viruses and liposomes, we have developed new methods to synthesize novel miR-30c analogs with increasing potency and efficacy, including 2'-O-methyl (2'OMe), 2'-fluoro (2'F), pseudouridine (ᴪ), phosphorothioate (PS), and N-acetylgalactosamine (GalNAc). The discovery of these modifications has profoundly impacted the modern RNA therapeutics, as evidenced by their increased nuclease stability and reduction in immune responses. We show that modifications on the passenger strand of miR-30c not only stabilize the duplex but also aid in a more readily uptake by the cells without the aid of viral vectors or lipid emulsions. After uptake, the analogs with PS linkages and GalNAc-modified ribonucleotides significantly reduce the secretion of apolipoprotein B (ApoB) without affecting apolipoprotein A1 (ApoA1) in human hepatoma Huh-7 cells. We envision an enormous potential for these modified miR-30c analogs in therapeutic intervention for treating cardiovascular diseases. J Biol Chem (2021), DOI: 10.1016/j.jbc.2022.101813.
Citation
Zheng YY, Haruehanroengra P, Yadav PK, Irani S, Mao S, Wang T, Hussain MM, Sheng J. Synthesis of Novel MicroRNA-30c Analogs to Reduce Apolipoprotein B Secretion in Human Hepatoma Cells. Bio Protoc. 2022 Dec 20;12(24):e4574. doi: 10.21769/BioProtoc.4574. PMID: 36618093; PMCID: PMC9797360.