Comparative transduction efficiencies of human and nonhuman adenoviral vectors in human, murine, bovine, and porcine cells in culture
Comparative transduction efficiencies of human and nonhuman adenoviral vectors in human, murine, bovine, and porcine cells in culture
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DOI：
10.1016/j.bbrc.2004.12.099
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发表时间：
2005-02-18
影响因子：
3.1
通讯作者：
Mittal, SK
中科院分区：
文献类型：
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作者：
Bangari, DS;Shukla, S;Mittal, SK
基于人类 Ad 血清型 5 (HAd5) 的载体的临床用途受到限制，主要是因为预先存在的 Ad 免疫性和缺乏针对特定细胞类型的靶向性。基于不太流行的 HAd 血清型以及非人类腺病毒（例如猪 Ad 血清型 3 (PAd3) 和牛 Ad 血清型 3 (BAd3)）的替代载体正在开发中，以克服这些缺点。使用病毒中和试验，我们检查了人类中预先存在的 Ad 免疫是否会交叉中和 PAd3 或 MO。为了进一步评估 PAd3 和 BAd3 载体作为基因递送载体的潜力，我们将它们在一组人、鼠、牛和猪细胞系中的转导效率与使用 HAd5 载体获得的转导效率进行了比较。 HAd5 载体在大多数人类细胞系中的转导与柯萨奇病毒腺病毒受体 (CAR)（主要 HAd5 受体）的表达水平相关；而PAd3和BAd3载体的转导是不依赖于CAR的。结果表明，PAd3 和 BAd3 载体是用于人类基因治疗以及人类和动物重组疫苗的有前景的基因递送载体。 (C) 2004 Elsevier Inc. 保留所有权利。
Clinical usefulness of human Ad serotype 5 (HAd5) based vectors is limited primarily because of preexisting Ad immunity and lack of targeting to specific cell types. Alternative vectors based on less prevalent HAd serotypes as well as nonhuman adenoviruses such as porcine Ad serotype 3 (PAd3) and bovine Ad serotype 3 (BAd3) are being developed to overcome these shortcomings. Using virus neutralization assay, we examined whether preexisting Ad immunity in humans would cross-neutralize PAd3 or MO. To further evaluate the potential of PAd3 and BAd3 vectors as gene delivery vehicles, we compared their transduction efficiencies in a panel of human, murine, bovine, and porcine cell lines to those obtained with a HAd5 vector. Transduction by the HAd5 vector in the majority of human cell lines correlated with the expression levels of coxsackievirus-adenovirus receptor (CAR), the primary HAd5 receptor; while transduction by PAd3 and BAd3 vectors was CAR-independent. The results suggest that PAd3 and BAd3 vectors are promising gene delivery vehicles for human gene therapy as well as for recombinant vaccines for human and animal use. (C) 2004 Elsevier Inc. All rights reserved.