Gene delivery to mitochondria by targeting modified adenoassociated virus suppresses Leber's hereditary optic neuropathy in a mouse model

Hong Yu, Rajeshwari D. Koilkonda, Tsung Han Chou, Vittorio Porciatti, Sacide S. Ozdemir, Vince Chiodo, Sanford L. Boye, Shannon E. Boye, William W. Hauswirth, Alfred S. Lewin, John Guy

Research output: Contribution to journalArticle

97 Scopus citations


To introduce DNA into mitochondria efficiently, we fused adenoassociated virus capsid VP2 with a mitochondrial targeting sequence to carry the mitochondrial gene encoding the human NADH ubiquinone oxidoreductase subunit 4 (ND4). Expression of WT ND4 in cells with the G11778A mutation in ND4 led to restoration of defective ATP synthesis. Furthermore, with injection into the rodent eye, human ND4 DNA levels in mitochondria reached 80% of its mouse homolog. The construct expressed in most inner retinal neurons, and it also suppressed visual loss and optic atrophy induced by a mutant ND4 homolog. The adenoassociated virus cassette accommodates genes of up to ∼5 kb in length, thus providing a platform for introduction of almost any mitochondrial gene and perhaps even allowing insertion of DNA encompassing large deletions of mtDNA, some associated with aging, into the organelle of adults.

Original languageEnglish
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number20
StatePublished - May 15 2012


ASJC Scopus subject areas

  • General

Cite this