Long-term enzyme correction and lipid reduction in multiple organs of primary and secondary transplanted Fabry mice receiving transduced bone marrow cells.
Long-term enzyme correction and lipid reduction in multiple organs of primary and secondary transplanted Fabry mice receiving transduced bone marrow cells.
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对接受转导骨髓细胞的初次和二次移植法布里小鼠的多个器官进行长期酶校正和脂质减少。
DOI：
10.1073/pnas.120177997
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发表时间：
2000
影响因子：
11.1
通讯作者：
Medin,JA
中科院分区：
文献类型：
--
作者：
Takenaka,T;Murray,GJ;Qin,G;Quirk,JM;Ohshima,T;Qasba,P;Clark,K;Kulkarni,AB;Brady,RO;Medin,JA
法布里病是一个引人注目的目标基因治疗作为一种治疗策略。溶酶体水解酶α-半乳糖苷酶A（α-gal A; EC 3.2.1.22）的缺乏会导致α-半乳糖基末端脂质（例如球三己糖神经酰胺（Gb 3））的分解代谢受损。患者发生血管闭塞，导致心血管、脑血管和肾脏疾病。与某些溶酶体贮积症不同，法布里病的原发神经系统受累有限。酶缺陷可以通过基因转移来纠正。通过转导细胞过表达α-gal A导致该酶的分泌。分泌的酶可能通过受体介导的内吞作用被非转导细胞摄取。在酶在血液中循环后，旁观者细胞的纠正可局部或全身发生。本文报道了α-gal A缺陷小鼠Fabry病模型的长期遗传校正研究。用编码α-gal A的逆转录病毒转导α-gal A缺陷的骨髓单个核细胞（BMMCs），并将其移植到亚致死和致死照射的α-gal A缺陷小鼠体内。分析血浆、外周血单核细胞、BMMC、肝、脾、心、肺、肾和脑中的α-gal A活性和Gb 3水平。对主要受体动物进行长达26周的随访。然后将BMMC移植到第二受体中。除脑外，所有受体组的所有器官和组织中均观察到α-gal A活性增加和Gb 3储存减少。即使在低百分比的转导细胞中也会发生这些效应。研究结果表明，遗传校正的骨髓细胞来源于法布里病患者可能有效用的表型校正这种疾病的患者。
Fabry disease is a compelling target for gene therapy as a treatment strategy. A deficiency in the lysosomal hydrolase α-galactosidase A (α-gal A; EC 3.2.1.22) leads to impaired catabolism of α-galactosyl-terminal lipids such as globotriaosylceramide (Gb3). Patients develop vascular occlusions that cause cardiovascular, cerebrovascular, and renal disease. Unlike for some lysosomal storage disorders, there is limited primary nervous system involvement in Fabry disease. The enzyme defect can be corrected by gene transfer. Overexpression of α-gal A by transduced cells results in secretion of this enzyme. Secreted enzyme is available for uptake by nontransduced cells presumably by receptor-mediated endocytosis. Correction of bystander cells may occur locally or systemically after circulation of the enzyme in the blood. In this paper we report studies on long-term genetic correction in an α-gal A-deficient mouse model of Fabry disease. α-gal A-deficient bone marrow mononuclear cells (BMMCs) were transduced with a retrovirus encoding α-gal A and transplanted into sublethally and lethally irradiated α-gal A-deficient mice. α-gal A activity and Gb3 levels were analyzed in plasma, peripheral blood mononuclear cells, BMMCs, liver, spleen, heart, lung, kidney, and brain. Primary recipient animals were followed for up to 26 weeks. BMMCs were then transplanted into secondary recipients. Increased α-gal A activity and decreased Gb3 storage were observed in all recipient groups in all organs and tissues except the brain. These effects occurred even with a low percentage of transduced cells. The findings indicate that genetic correction of bone marrow cells derived from patients with Fabry disease may have utility for phenotypic correction of patients with this disorder.
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源自转导骨髓细胞的循环 α-半乳糖苷酶 A：与法布里病校正基因转移的相关性。
影响因子：
4.2
作者：
T. Takenaka;G. Qin;R. Brady;J. Medin
通讯作者：
J. Medin
DOI：
10.1073/pnas.94.6.2540
发表时间：
1997-03-18
影响因子：
11.1
作者：
Ohshima, T;Murray, GJ;Kulkarni, AB
通讯作者：
Kulkarni, AB
DOI：
10.1073/pnas.93.15.7917
发表时间：
1996-07-23
影响因子：
11.1
作者：
Medin, JA;Tudor, M;Brady, RO
通讯作者：
Brady, RO
小鼠肌肉中人α-半乳糖苷酶的体内外基因转移和表达
影响因子：
5.1
作者：
FJ Novo;D. Górecki;G. Goldspink;K. Macdermot
通讯作者：
K. Macdermot
造血干细胞和内皮细胞的遗传标记
DOI：
--
发表时间：
2006
期刊：
Identification of the Tmtsp genes encoding a novel cell-surface protein with the thrombospondin-1 domain 107
影响因子：
--
作者：
Takayanagi;S.;Hiroyama;T.;Yamazaki;S.;Nakajima;T.;Morita;Y.;Usui;J.;Eto;K.;Motohashi;T.;Shiomi;K.;Keino-Masu;K.;Masu;M.;Oike;Y.;Mori;S.;Yoshida;N.;Iwama;A.and Nakauchi;H
通讯作者：
H