CMCOs are the only antisense concept that is also effective in mitochondria

Mitochondria are the power centres of the cell. The existence of its own DNA and gene expression system makes mitochondria an ideal target for a gene silencing approach. Mitochondria carry their own DNA (mitochondrial DNA, mtDNA) and are surrounded by two membranes. The inner mitochondrial membrane is even harder to penetrate than the cell membrane, making it an insurmountable barrier to all competing antisense approaches.

The CMCOs can chemically be modified in such a manner that they selectively accumulate in mitochondria once they have entered the cell.

Fluorescence microscopy of HeLa cells treated with biotinylated CMCOs (green staining) shows a clear and exclusive co-localisation of CMCOs and mitochondria (red staining detected by MitoTracker). The cell nucleus is detected using DAPl (blue staining).

Human cells contain thousands of copies of mtDNA, which encodes 13 essential proteins, 22 transfer RNAs (tRNA) and 2 ribosomal RNAs (rRNA).

Mutations of the mtDNA have been linked with a variety of progressive clinical disorders such as rare hereditary diseases, diabetes or cancer. Up to now there is no effective treatment for disorders caused by mutations of mitochondrial DNA.

CMCOs are the first and only antisense concept that has also been shown to be effective in mitochondria by reducing mtDNA expression.