Adenosine Deaminases Acting on RNA (ADAR) enzymes catalyse the conversion of adenosine (A) to inosine (I) within double-stranded RNA (dsRNA) molecules. This mechanism, known as A-I RNA editing, is able to modulate gene expression, RNA stability and protein function.Recently, new therapeutic approaches based on site-directed RNA editing (SDRE) leverage the recoding ability of ADAR to correct pathogenic G to A nucleotide mutations. SDRE allows for the manipulation of genetic information without causing damage to the genome. G-to-A point mutations make up nearly 30% of the pathogenic single nucleotide variations in the human genome and can be potentially targeted by ADAR mediated repair.In order to study the possible therapeutic implications of these enzymes, we have selected two mutations: the LRRK2 p.G2019S, that is one of the most common genetic determinants of Parkinson’s Disease (PD) and the TDP43 p.A382T, a genetic variant of the TAR DNA-binding protein 43 (TDP-43) gene, which has been associated with Amyotrophic Lateral Sclerosis.The goal of the project is to identify the most effective guide RNAs to recruit endogenous ADAR enzymes to the specific point mutations. Our preliminary experiments showed that it is possible to revert the LRRK2 p.G2019S G-to-A mutation in HEK293T cells transfected with the mutated version of LRRK2, ADAR1 enzymes and a specific ADAR recruiting guide RNA. These data demonstrate the importance of deepening the role of ADAR enzymes in therapy.