Nucleic Acids Research, 1995, Vol. 23, No. 1 10-17
© 1995
MOLECULAR BIOLOGY |
Transfection of mitochondria: strategy towards a gene therapy of mitochondrial DNA diseases
1Department of Neurology Josef-Schneider-Straße 11, 97080 Wurzburg, Germany 2Institute of Medical Biochemistry and Chemistry Piazza G. Cesare, 70124 Ban, Italy
*To whom correspondence should be addressed
Received . Revised November 24, 1994. Accepted November 24, 1994.
Successes in classical gene therapies have been achieved by placing a corrected copy of a defective nuclear gene in cells. A similar gene replacement approach for a mutant mitochondrial genome is invariably linked to the use of a yet unavailable mitochondrial transfection vector. Here we show that DNA coupled covalently to a short mitochondrial leader peptide (chimera) can enter mitochondria via the protein import pathway, opening a new way for gene-, antisense-RNA-or antisense-DNA-delivery in molecular therapies. The import behavior of the purified chimera, composed of the amino-terminal leader peptide of the rat ornithine transcarbamylase (OTC) and a double stranded DNA molecule (17 bp or 322 bp), was tested by incubating with coupled and "energized" rat liver mitochondria in the presence of reticulocyte lysate. The chimera was translocated with a high efficiency into the matrix of mitochondria utilizing the protein import pathway, independent from the size of its passenger DNA.
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