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However, tailored medications for extremely rare disorders (N-of-1) offer a ray of hope. Artificial antisense oligonucleotides (ASOs) are now best known for their use in spinal muscular atrophy (SMA). The success of nusinersen\/Spinraza for SMA indicates the potential of ASO therapies for other rare conditions. We propose a strategy to develop N-of-1 ASOs for treating one form of trichothiodystrophy (TTD), a rare condition with multisystem abnormalities and reduced life expectancy, associated with instability and greatly reduced amounts of the DNA-repair\/transcription factor TFIIH. The therapeutic targets carry mutations in\n                    <jats:italic>GTF2H5<\/jats:italic>\n                    , encoding the TFIIH-p8 subunit. This approach was inspired by the diagnosis and molecular dissection of a xeroderma pigmentosum (XP) case with mutations in\n                    <jats:italic>GTF2H4<\/jats:italic>\n                    , encoding the TFIIH-p52 subunit. This is newly classified as a ninth XP complementation\u2013group, XP-J, identified 5 decades after the discovery of the other XP complementation\u2013groups. The p8-p52 interaction is required to support the TFIIH-complex formation, and the patient\u2019s p52 C-terminal truncation results in the complete absence of p8 in TFIIH. However, intriguingly, TFIIH remained stable in vivo, and the patient with XP-J did not exhibit any TTD-features. The aim of our ASO-design is to induce a C-terminal truncation of p52 and we have successfully stabilized TFIIH in p8-deficient cells from patients with TTD-A.\n                  <\/jats:p>","DOI":"10.1172\/jci195732","type":"journal-article","created":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T16:00:43Z","timestamp":1757433643000},"source":"Crossref","is-referenced-by-count":5,"title":["TFIIH-p52\u0394C defines a ninth xeroderma pigmentosum complementation\u2013group XP-J and restores TFIIH stability to p8-defective trichothiodystrophy"],"prefix":"10.1172","volume":"135","author":[{"given":"Yuka","family":"Nakazawa","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Japan."},{"name":"Department of Genetics, Research Institute of Environmental Medicine (RIeM), Nagoya University, Nagoya, 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