Correction of clinical manifestations of canine mucopolysaccharidosis I with neonatal retroviral vector gene therapy.
Correction of clinical manifestations of canine mucopolysaccharidosis I with neonatal retroviral vector gene therapy.
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用新生儿逆转录病毒载体基因治疗纠正犬粘多糖贮积症I的临床表现。
DOI：
10.1038/sj.mt.6300201
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Ponder,KatherineP
中科院分区：
文献类型：
--
作者：
Traas,AnneM;Wang,Ping;Ma,Xiucui;Tittiger,Mindy;Schaller,Laura;O'donnell,Patricia;Sleeper,MegM;Vite,Charles;Herati,Ramin;Aguirre,GustavoD;Haskins,Mark;Ponder,KatherineP
粘多糖病I(MPS I)又称赫尔勒综合征，是由于α-L-艾杜糖苷酶活性低下所致，是最常见的MPS疾病之一。新生的MPS I犬静脉注射含有完整长末端重复序列(LtR)和犬IDUA互补基因上游的人α1抗胰蛋白酶(HAAT)启动子的伽玛逆转录病毒载体。这导致血清IDUA活性在长达1.8年的时间内稳定在366±344单位(U)/ml(28倍正常)，这可能主要来自转导的肝细胞分泌IDUA。与未经治疗的MPS I犬相比，经逆转录病毒载体(RV)治疗的犬的脏器IDUA活性为正常的18%，并降低了疝气、胸部畸形、关节疾病、面部变形、角膜混浊、瓣膜心脏病和主动脉扩张的严重程度和/或发生率。在接受RV治疗的狗的大脑中观察到的溶酶体存储显著减少的部分原因可能是由于载体在大脑细胞中的LTR表达。这种可能性将在未来的研究中进行探索，因为插入突变的可能性已经引起了人们对使用具有完整LTR的载体的担忧。如果被证明是安全的，这种基因治疗技术可能被用于治疗儿童赫勒综合征。
Mucopolysaccharidosis I (MPS I) (Hurler syndrome) is due to deficientα-l-iduronidase (IDUA) activity and is the most common of the MPS disorders. Neonatal MPS I dogs were injected intravenously (IV) with a gamma retroviral vector containing a complete long-terminal repeat (LTR) and an internal humanα1-antitrypsin (hAAT) promoter upstream of the canine IDUA complementary DNA (cDNA). This resulted in stable serum IDUA activity of 366 ± 344 units (U)/ml (28-fold normal) for up to 1.8 years, which likely derived primarily from secretion of IDUA by transduced liver cells. Retroviral vector (RV)-treated dogs had >18% of normal IDUA activity in organs and had decreased severity and/or incidence of hernias, chest deformities, joint disease, facial dysmorphia, corneal clouding, valvular heart disease, and aortic dilatation as compared with untreated MPS I dogs. The marked reduction that was observed in lysosomal storage in the brain of RV-treated dogs may have been due in part to expression from the LTR of the vector in cells in the brain. This possibility will be explored in future studies, because the potential for insertional mutagenesis has raised concerns about using vectors with an intact LTR. If proven safe, this gene therapy technique may be utilized in treating children with Hurler syndrome.
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Hurler 综合征犬模型中的酶替代。
DOI：
10.1073/pnas.91.26.12937
发表时间：
1994
影响因子：
11.1
作者：
Shull,RM;Kakkis,ED;McEntee,MF;Kania,SA;Jonas,AJ;Neufeld,EF
通讯作者：
Neufeld,EF
表达人类因子 IX 的逆转录病毒载体在狗、猫和小鼠中进行新生儿移植后的免疫反应。
影响因子：
7.5
作者：
Xu,Lingfei;Mei,Manxue;Haskins,MarkE;Nichols,TimothyC;O'donnell,Patricia;Cullen,Karyn;Dillow,Aaron;Bellinger,Dwight;Ponder,KatherineP
通讯作者：
Ponder,KatherineP
血细胞中的表达可能有助于狗新生儿静脉内基因治疗粘多糖贮积症 VII 后的生化和病理学改善。
影响因子：
3.8
作者：
Wang,Bin;O'Malley,ThomasM;Xu,Lingfei;Vite,Charles;Wang,Ping;O'Donnell,PatriciaA;Ellinwood,NMatthew;Haskins,MarkE;Ponder,KatherineParker
通讯作者：
Ponder,KatherineParker
影响因子：
158.5
作者：
Kakkis, ED;Muenzer, J;Thompson, JN
通讯作者：
Thompson, JN
犬α-L-艾杜糖酸酶缺乏症的基因治疗：基因校正的造血祖细胞在子宫内过继转移导致植入，但不能改善疾病。
影响因子：
4.2
作者：
Carolyn Lutzko;Fusayuki Omori;A. Abrams;Robert M. Shull;Liheng Li;K. Lau;Christine Ruedy;S. Nanji;Cathy Gartley;H. Dobson;Robert A. Foster;Stephen A. Kruth;Ian D. Dubé
通讯作者：
Ian D. Dubé