Gene delivery with a novel mitochondrial transmembrane peptide

November 1, 2023

Efficient multigene expression in mitochondria achieved

A joint research group of RIKEN CSRS, Kyoto University, Keio University, and others has discovered that complexes consisting of plasmid DNA (pDNA) and a functional peptide inspired by mitochondrial membrane proteins selectively accumulate in the mitochondria in cells, and lead to efficient gene expression within the mitochondria.

In this study, the group transfected mitochondria-targeting complexes consisting of a functional peptide (mitoNEET-(RH)9) containing a partial sequence of a mitochondrial transmembrane protein (mitoNEET) and pDNA or mitochondrial DNA (mtDNA) into cells, and found that the complexes were selectively accumulated in the mitochondria. mtDNA delivered by the developed system induces sufficient gene expression to restore mitochondrial function in mtDNA-depleted cells.

The achievements in this study allow the expression of any proteins in the mitochondria and contribute to elucidating mechanisms of mitochondrial diseases, developing its therapeutics, and also establishing mtDNA editing technology.

Original article
Advanced Functional Materials doi: 10.1002/adfm.202306070
N. Yoshinaga, T. Miyamoto, M. Odahara, N. Takeda-Kamiya, K. Toyooka, S. Nara, H. Nishimura, F. Ling, M. Su'etsugu, M. Yoshida, K. Numata,
"Design of an artificial peptide inspired by transmembrane mitochondrial protein for escorting exogenous DNA into the mitochondria to restore their functions by simultaneous multiple gene expression".
Keiji Numata; Team Leader
Naoto Yoshinaga; Special Postdoctoral Researcher
Biomacromolecules Research Team