Modified vectors for organelle transfection

A composition comprising:

• a recombinant polypeptide comprising an organelle localization signal operably linked to a protein transduction domain, wherein the recombinant polypeptide is operably linked to a polynucleotide.

A method for treating a mitochondrial disease comprising contacting at least one cell of a host having or suspected of having a mitochondrial disease with a vector comprising at least one protein transduction domain on a surface of the vector, at least one mitochondrial targeting signal on a surface of the vector, and a polynucleotide encoding a functional mitochondrial polypeptide, wherein the functional mitochondrial polypeptide is expressed in at least one mitochondrion of the cell.

A method for producing a mtDNA depleted cell comprising:

• contacting the cell with at least one siRNA directed to POLγ.

A kit for transfecting organelles, the kit comprising:

• a polynucleotide encoding an organelle localization signal operably linked to a bacteriophage lambda surface polypeptide;
• and bacteriophage lambda packaging components for preparing a recombinant lambda vector.

A method for transfecting an organelle, the method comprising the step of introducing a recombinant viral vector comprising a nucleic acid to be expressed in the organelle into the cytosol of a cell, wherein the recombinant viral vector displays an organelle localization signal on a surface of the vector for directing the vector to an organelle to be transfected.

A method for producing a cell lacking mitochondrial DNA comprising:

• contacting the cell with at least one siRNA directed to a gene involved in sustaining or maintaining mtDNA or mtDNA stability.