Development of a nanoparticle that releases nucleic acids in response to a mitochondrial environment

Mitochondrion. 2020 May:52:67-74. doi: 10.1016/j.mito.2020.02.009. Epub 2020 Feb 22.

Abstract

The delivery of nucleic acids targeting mutant mtDNA represent a potential strategy for addressing a variety of mitochondria-related diseases. We previously developed a MITO-Porter, a nano carrier that is capable of delivering nanoparticles of nucleic acids to mitochondria of human cells. Here, we report on an investigation of a series of nanoparticles formed with various poly cationic peptides that can release nucleic acids in response to a mitochondrial environment. A significant relationship was found between the number of and the location of arginine and histidine residues in the peptide sequence and the release of nucleic acids in a mitochondrial environment.

Keywords: Mitochondria; Mitochondrial environment-response; Nanoparticle formation; Nucleic acid medicine; Nucleic acid nanoparticle; Nucleic acid release.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Arginine / chemistry
  • Cell Line
  • DNA, Mitochondrial / drug effects*
  • DNA, Mitochondrial / genetics
  • Histidine / chemistry
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects
  • Mitochondria / genetics*
  • Mutation
  • Nanoparticles
  • Peptides / chemistry*
  • RNA / chemistry
  • RNA / pharmacology*

Substances

  • DNA, Mitochondrial
  • Peptides
  • Histidine
  • RNA
  • Arginine