Absence of germline infection in male mice following intraventricular injection of adenovirus.

Absence of germline infection in male mice following intraventricular injection of adenovirus.
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雄性小鼠脑室内注射腺病毒后不存在种系感染。

DOI:
10.1006/mthe.2001.0500
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发表时间:
2001
期刊:
Molecular therapy : the journal of the American Society of Gene Therapy
影响因子:
--
通讯作者:
Robert E. Braun
Robert E. Braun
中科院分区:
--
文献类型:
--
作者:
Antoine H.F.M. Peters;Jeff Drumm;Carolyn Ferrell;David A. Roth;David M. Roth;Michael McCaman;Patricia L. Novak;Jeffrey Friedman;Robert L. Engler;Robert E. Braun

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性腺组织无意中暴露于基因治疗载体的可能性引起了对生殖系感染的安全担忧。我们在这里发现柯萨奇B病毒和腺病毒2和5的受体(CXADR)在小鼠生殖细胞中表达,提示这些病毒可能感染生殖细胞。为了直接评估体内种系感染的风险,我们将携带与细菌lacZ报告基因融合的生殖细胞特异性鱼精蛋白启动子的腺病毒注射到小鼠左心室腔,然后监测该报告基因在生殖细胞中的表达。为了区分干细胞感染和分化的生精细胞,我们分析了病毒传递后不同时间报告磁带的表达。在所有测试条件下,小鼠在发育中的精子或成熟的附睾精子中均未表达大肠杆菌β -半乳糖苷酶蛋白。体外培养的原代生殖细胞对腺病毒感染也不耐。我们的数据表明,在冠状动脉内腺病毒传递后,垂直种系传播和插入突变的机会是极不可能的。
The possibility of inadvertent exposure of gonadal tissue to gene therapy vectors has raised safety concerns about germline infection. We show here that the receptor for coxsackie B viruses and adenoviruses 2 and 5 (CXADR) is expressed in mouse germ cells, suggesting the possibility that these viruses could infect germ cells. To directly assess the risk of germline infection in vivo, we injected an adenovirus carrying the germ-cell-specific protamine promoter fused to the bacterial lacZ reporter gene into the left ventricular cavity of mice and then monitored expression of the reporter gene in germ cells. To differentiate between infection of stem cells and differentiating spermatogenic cells, we analyzed expression of the reporter cassette at different times after viral delivery. Under all conditions tested, mice did not express the Escherichia coli beta-galactosidase protein in developing spermatids or in mature epididymal spermatozoa. Primary germ cells cultured in vitro were also refractory to adenoviral infection. Our data suggest that the chance of vertical germline transmission and insertional mutagenesis is highly unlikely following intracoronary adenoviral delivery.
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