A nanocarrier for the mitochondrial delivery of nucleic acids to cardiomyocytes. (20th February 2020)

• Record Type: Journal Article
• Authors: Yamada, Yuma; Fujishita, Naoki; Harashima, Hideyoshi
• Is Part Of: Nucleosides, nucleotides & nucleic acids. Volume 39:Number 1-3(2020)
• Page Start: 141
• Page End: 155
• Publication Date: 2020-02-20
• Subjects: Cardiac myoblasts -- mitochondria -- nucleic acids delivery -- liposomes -- mitochondrial delivery -- multifunctional envelope-type nano device (MEND); Nucleosides -- Periodicals; Nucleotides -- Periodicals; Nucleic acids -- Periodicals; 572.8
• DOI: 10.1080/15257770.2019.1675167
• Languages: English
• ISSNs: 1525-7770

Abstract

Abstract: Cardiomyopathy caused by mitochondrial dysfunction associated with the mutation/deletion of mitochondrial DNA has been reported, and nucleic acid therapy targeting cardiac mitochondria represents a possible therapy for treating these diseases. Such a treatment, however, has not yet been achieved because delivering nucleic acids to mitochondria of cardiac muscle is difficult. In this study, H9c2 cells a type of rat cardiac myoblasts, were used as model cardiac muscle cells. The use of a lipid composition used to prepare the β-MEND (where MEND denotes multifunctional envelope-type nano device) permitted the particles to be efficiently internalized by H9c2 cells, as evidenced by flow cytometry analyses. Intracellular observations by confocal laser scanning microscopy showed that the β-MEND efficiently accumulated in mitochondria of H9c2 cells. We also constructed an RP/β-MEND that contained a mitochondrial RNA aptamer to achieve mitochondrial delivery in H9c2 cells. The successful direct mitochondrial transfection of exogenous RNA was confirmed using these carrier systems, based on PCR experiments after reverse transcription. Thus, the β-MEND holds promise as a direct mitochondrial transfection system for delivering nucleic acids targeted to H9c2 cells.