The present invention relates to methods and means for producing nitrogenase polypeptides in the mitochondria of plant cells.

The present invention relates to new Transcription Activator-Like Effector proteins and more particularly new Transcription Activator-Like Effector Nucleases (TALENs) that can efficiently target and process nucleic acids. The present invention also concerns methods to use these new Transcription Activator-Like Effector proteins. The present invention also relates to vectors, compositions and kits in which Transcription Activator-Like Effector proteins of the present invention are used.

Disclosed herein are recombinant meganucleases engineered to bind and cleave a recognition sequence in the mitochondrial DNA (mtDNA) of a eukaryotic cell, such as a plant cell. The disclosure further relates to the use of such recombinant meganucleases in methods for producing genetically-modified eukaryotic cells, and to a population of genetically-modified eukaryotic cells wherein the mtDNA has been having modified or edited.

Compositions and methods for mitochondria genome editing are provided. Also provided are methods for treating mitochondrial disorders by the disclosed compositions.

The invention encompasses water-forming NADH and NADPH oxidases and the use of these enzymes to treat mammalian diseases or conditions associated with an elevated NADH/NAD.sup.+ ratio or NADPH/NADP+ ratio. Such pathologies include disorders caused by one or more defects in the mitochondrial respiratory chain, glucose metabolism disorders, cancers associated with reductive stress, and aging. The invention also provides a research tool for investigating the effect of exogenous water-forming NADH or NADPH oxidases on the metabolism of a mammalian cell, such as a human cell, and for elucidating the role of respiratory chain proteins in mitochondrial disorders.

Disclosed are novel fusion protein constructs comprising a functional mitochondrial protein, that can enter mitochondria within intact cells. Further disclosed are methods of treating mitochondrial disorders by the disclosed fusion proteins and compositions therefor.

The invention relates, in part, to compounds, compositions, and methods useful to treat cancer in cells and subjects. In some aspects the invention includes contacting a cancer cell with one or more exogenous methylation-controlled J protein (MCJ) agonist compounds to increase sensitivity of the cancer cell to one or more chemotherapeutic agents. In certain aspects the invention includes compounds and methods useful to kill cancer cells.

Disclosed herein are recombinant meganucleases engineered to recognize and cleave a recognition sequence present in the human mitochondrial DNA (mtDNA). The disclosure further relates to the use of such recombinant meganucleases in combination with mitochondrial transit peptides in methods for producing genetically-modified eukaryotic cells, and to a population of genetically-modified eukaryotic cells wherein the mtDNA has been modified or edited.

It is an object of the present invention to provide a method for editing or modifying plant genomes (a nuclear genome, a plastid genome, and a mitochondrial genome), and in particular, the editing or modification of a single nucleotide. Specifically, the present invention relates to a method for editing genomic DNAs in plant cells, namely, a nuclear genomic DNA, a plastid genomic DNA and a mitochondrial genomic DNA, wherein the method comprises converting target nucleotides on these genomic DNAs to other nucleotides. This conversion is carried out, for example, with cytidine deaminase, and in particular, with the aforementioned enzyme using a double-stranded DNA as a substrate.

Disclosed are fusion protein constructs comprising a functional mitochondrial protein, that can enter mitochondria within intact cells. Further disclosed are methods of treating mitochondrial disorders by the disclosed fusion proteins and compositions therefor.