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.

Inclusion Criteria:

• 18 ≤ age ≤ 70 years.
• Signed written, free and informed consent to participate in the study.
• Patients with a CAG≥36 allele (with reduced or full penetrance). penetrance)
• People affiliated to or benefiting from a social security scheme.

Exclusion Criteria:

• Individuals who have participated in a gene therapy trial using AAV, ASO, mi/si/shRNA administration, likely to disrupt expression, splicing of pre-mRNAs, mRNA splicing, mRNA expression/regulation/translation, energy or protein metabolism directly or indirectly linked to the Huntingtin gene (HTT), its transcripts and proteins.
• Clinical or paraclinical elements that may suggest a differential diagnosis.
• People unable to express their consent.
• Pregnant, breast-feeding or parturient women
• People deprived of liberty by administrative or judicial decision
• People under legal protection (curatorship, guardianship).