Targeted mitochondrial delivery of antisense RNA-containing nanoparticles by a MITO-Porter for safe and efficient mitochondrial gene silencing

Eriko Kawamura; Mitsue Hibino; Hideyoshi Harashima; Yuma Yamada

doi:10.1016/j.mito.2019.08.004

Targeted mitochondrial delivery of antisense RNA-containing nanoparticles by a MITO-Porter for safe and efficient mitochondrial gene silencing

Mitochondrion. 2019 Nov:49:178-188. doi: 10.1016/j.mito.2019.08.004. Epub 2019 Aug 28.

Authors

Eriko Kawamura¹, Mitsue Hibino¹, Hideyoshi Harashima¹, Yuma Yamada²

Affiliations

¹ Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
² Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan. Electronic address: u-ma@pharm.hokudai.ac.jp.

PMID: 31472283
DOI: 10.1016/j.mito.2019.08.004

Abstract

Mitochondrial gene therapy will be needed to treat mitochondrial diseases. We previously demonstrated mitochondrial gene silencing by the mitochondrial delivery of antisense RNA oligonucleotide (ASO) targeting mtDNA-encoded mRNA using a MITO-Porter, a liposomal nano carrier system designed for mitochondrial delivery. Here, we report on the efficient packaging of ASO in the MITO-Porter via a nanoparticle packaging method, which showed a 10-fold higher packaging efficiency than the conventional method. The constructed carrier showed a decrease in the target mRNA levels and ATP production. These results indicate that such a MITO-Porter has potential for use in therapies designed to regulate mitochondrial function.

Keywords: MITO-porter; Mitochondrial RNA knockdown; Mitochondrial drug delivery; Nucleic acids delivery; Nucleic acids medicine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Gene Silencing*
Gene Transfer Techniques*
Genes, Mitochondrial*
HeLa Cells
Humans
Mitochondria* / genetics
Mitochondria* / metabolism
Nanoparticles / chemistry*
RNA, Antisense* / chemistry
RNA, Antisense* / genetics
RNA, Antisense* / pharmacology

Substances

RNA, Antisense