Development of nucleic acid molecules aimed at recovering mitochondrial dysfunction in cancer and neurodegenerative diseases.

The project aims to develop new therapeutic strategiesbased on targeting the mitochondrial protein VDAC intumours and neurodegenerative diseases. The firstobjective is to interfere with the VDAC-Hexokinase-1(HK1) complex, which plays a central role in both themitochondrial dysfunction associated withneurodegeneration and the metabolic advantage andresistance to apoptosis exhibited by cancer cells. To thisend, RNA molecules encoding interfering peptides willbe developed, including the NHK1 sequence, apatented peptide. The second objective is to reduceVDAC overexpression through the use of lncRNAs orcircRNAs derived from VDAC pseudogenes, in particularthe VDAC1P8 pseudogene, which has beencharacterized in acute myeloid leukaemia. Themolecules will be delivered via LNPs functionalised fortissue targeting or via suitable viral vectors.