Huntington's disease is a rare and fatal monogenic neurodegenerative disorder whose molecular origin is an expansion of CAG triplets within the first exon of the Huntingtin gene. Although a growing number of emerging therapies are in clinical trials, there are no proven neuroprotective or curative treatments approved by the health authorities, as they have not yet demonstrated any real therapeutic benefit or absence of toxicity. Trans-splicing gene therapy is defined as the correction of a mutated endogenous pre-messenger RNA by a therapeutic exogenous pre-messenger RNA. Trans-splicing is a suitable alternative approach, since it is capable of allelic selectivity and replacement of mutated sequences by the wild-type one, criteria that no therapy tested to date meets. This project involves the therapeutic validation of trans-splicing of Huntingtin gene transcripts, and will evaluate its therapeutic effects in vitro, into primary fibroblast cell lines derived from skin biopsies of Huntington's disease patients.