Targeted delivery of DNA to the mitochondrial compartment via import sequence-conjugated peptide nucleic acid

被引:113
作者
Flierl, A
Jackson, C
Cottrell, B
Murdock, D
Seibel, P
Wallace, DC
机构
[1] Univ Calif Irvine, Ctr Mol & Mitochondrial Med & Genet, Irvine, CA 92697 USA
[2] Emory Univ, Ctr Mitochondrial Med, Atlanta, GA 30322 USA
[3] Res Genet, Huntsville, AL 35801 USA
[4] Univ Wurzburg, Biozentrum, Lehrstuhl Zell & Entwicklungsbiol, D-97074 Wurzburg, Germany
关键词
mitochondria; transformation; import; targeting peptide; peptide nucleic acid; drug delivery; oligonucleotide; gene therapy;
D O I
10.1016/S1525-0016(03)00037-6
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
We report that oligonucleoticles can be introduced into the mitochondria of living mammalian cells by annealing them to peptide nucleic acids coupled to mitochondrial targeting peptides. These complexes are imported into the mitochondrial matrix through the outer and inner membrane import channels of isolated mitochondria. They are also imported into the mitochondria of cultured cells, provided that the cytosolic uptake of the complexes is facilitated by using synthetic polycations or membrane permeabilizing toxins. Our method now promises to provide a viable strategy for the genetic modification of the mitochondria in cultured cells, animals and patients.
引用
收藏
页码:550 / 557
页数:8
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