New vector for therapy of mitochondrial disease

RNA targeting sequences to import oligonucleotides in the mitochondria.

TECHNOLOGY

• In human cells, a subset of small non-coding RNA is imported into mitochondria from the cytosol, including some tRNAs
• Identification of short synthetic RNAs domains of yeast tRNALysCUU (tRK1) alternative structure, D-arm or F-hairpin
• Fusion to oligonucleotides drive their mitochondrial import

APPLICATION

• Mitochondrial disease treatment using oligonucleotide based approaches (anti-replicative, antisense, gene editing)

INNOVATION ADVANTAGES

• Short RNA sequence able to internalize a therapeutic oligonucleotide
• Vector allows to suppress negative effects of point mutation and deletions in mtDNA

DEVELOPMENT STATUS

• In vitro POC using an anti-replicative approach showing a shift in heteroplasmy in a cellular model for Leigh Syndrome in Cybrid cell and patient’s fibroblast
• Preclinical POC program supported by Conectus under consideration