Antibody-directed targeting of retroviral vectors via cell surface antigens
Antibody-directed targeting of retroviral vectors via cell surface antigens
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DOI：
10.1128/jvi.75.17.8016-8020.2001
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发表时间：
2001-09-01
影响因子：
5.4
通讯作者：
Chen, ISY
中科院分区：
文献类型：
--
作者：
Morizono, K;Bristol, G;Chen, ISY
特异性细胞的靶向稳定转导是基因治疗应用的高度期望的目标。我们报告了一种有效的和广泛适用的方法靶向逆转录病毒载体的特定细胞。我们发现，甲病毒辛德毕斯病毒的包膜可以假型人类免疫缺陷病毒1型和小鼠白血病病毒为基础的逆转录病毒载体。当被修饰为含有蛋白A的Fc结合结构域时，相对于没有抗体，该包膜与HLA和CD4特异性抗体组合时特异性显著增强。与以前的逆转录病毒转导靶向策略不同，病毒滴度相对较高且稳定，并且可以通过超离心进一步增加。这项研究为靶向策略提供了原理证明，该靶向策略通常可用于许多基因治疗应用。
Targeted stable transduction of specific cells is a highly desirable goal for gene therapy applications. We report an efficient and broadly applicable approach for targeting retroviral vectors to specific cells. We find that the envelope of the alphavirus Sindbis virus can pseudotype human immunodeficiency virus type 1- and murine leukemia virus-based retroviral vectors. When modified to contain the Fc-binding domain of protein A, this envelope gives a significant enhancement in specificity in combination with antibodies specific for HLA and CD4 relative to that without antibody. Unlike previous targeting strategies for retroviral transduction, the virus titers are relatively high and stable and can be further increased by ultracentrifugation. This study provides proof of principle for a targeting strategy that would be generally useful for many gene therapy applications.