Mucopolysaccharidoses type I (MPS I) is an inherited metabolic disease characterized by a malfunction of the α-l-iduronidase (IDUA) enzyme leading to the storage of glycosaminoglycans in the lysosomes. This disease has longtime been studied as a therapeutic target for those studying gene therapy and many studies have been done using various vectors to deliver the IDUA gene for corrective treatment. Many vectors have difficulties with efficacy and insertional mutagenesis concerns including adeno-associated viral (AAV) vectors. Studies of AAV vectors treating MPS I have seemed promising, but recent deaths in gene therapy clinical trials for other inherited diseases using AAV vectors have left questions about their safety. Additionally, the recent modifications to adenoviral vectors leading them to target the vascular endothelium minimizing the risk of hepatotoxicity could lead to them being a viable option for MPS I gene therapy when coupled with gene editing technologies like CRISPR/Cas9.

中文翻译：

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粘多糖贮积症 I 型基因治疗

I 型粘多糖贮积症 (MPS I) 是一种遗传性代谢疾病，其特征是 α -l-艾杜糖醛酸酶 (IDUA) 酶功能障碍导致糖胺聚糖在溶酶体中的储存。这种疾病长期以来一直被研究作为研究基因治疗的治疗靶点，并且已经使用各种载体进行了许多研究来传递IDUA基因进行矫正治疗。许多载体在功效和插入诱变方面存在困难，包括腺相关病毒 (AAV) 载体。对 AAV 载体治疗 MPS 的研究似乎很有希望，但最近在使用 AAV 载体治疗其他遗传性疾病的基因治疗临床试验中出现的死亡事件引发了对其安全性的质疑。此外，最近对腺病毒载体的修改导致它们靶向血管内皮，从而最大限度地降低肝毒性的风险，这可能导致它们与 CRISPR/Cas9 等基因编辑技术相结合时成为 MPS I 基因治疗的可行选择。