Polypeptide targeting to mitochondria
AssigneeUnited Kingdom Research and Innovation
InventorsMichal Minczuk, Monika A. Papworth, Aaron Klug
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Abstract
Methods for delivering non-mitochondrial proteins to mitochondria are provided. Also provided are nucleic acid constructs comprising a coding sequence encoding a DNA-binding polypeptide, fused to a mitochondrial targeting sequence (MTS) and a nuclear export signal (NES), and the encoded proteins. The construct successfully delivers DNA binding proteins to the mitochondrion. A chimeric methylase based on the above construct is successfully delivered to mitochondria, resulting in modification of mtDNA.
Claims13
A fusion protein that binds to a point mutation in mutant mitochondrial DNA (mtDNA), the fusion protein comprising:
- (a) a zinc finger protein (ZFP) DNA-binding polypeptide comprising 3 zinc fingers, wherein the ZFP binds specifically to a target sequence in the mutant mtDNA, wherein the target sequence comprises the point mutation;
- (b) a functional domain which modifies the mutant mtDNA;
- (c) a mitochondrial targeting sequence (MTS);
- and
- (d) a nuclear export sequence (NES), wherein the fusion protein is localized in a mitochondria of a cell.
Dependencies are inferred from the claim text.