A chromatin insulator protects retrovirus vectors from chromosomal position effects
A chromatin insulator protects retrovirus vectors from chromosomal position effects
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DOI：
10.1073/pnas.160159597
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发表时间：
2000-08-01
影响因子：
11.1
通讯作者：
Stamatoyannopoulos, G
中科院分区：
文献类型：
--
作者：
Emery, DW;Yannaki, E;Stamatoyannopoulos, G
重组鼠逆转录病毒广泛用作基因治疗的递送载体。然而，一旦整合到染色体中，这些载体通常遭受深刻的位置效应，在体外和体内观察到载体沉默。为了克服这个问题，我们研究了来自鸡β-珠蛋白基因座中心区域的HS 4染色质绝缘子是否可以保护逆转录病毒载体免受位置效应的影响。当用于侧翼报告载体时，该元件显著增加了在培养物和移植有转导骨髓的小鼠中表达前病毒的转导细胞的分数。这些结果表明，染色质绝缘子可以通过保护这些载体免受染色体位置效应而改善广泛使用的一类基因治疗载体的表达性能。
Recombinant murine retroviruses are widely used as delivery vectors for gene therapy. However, once integrated into a chromosome, these vectors often suffer from profound position effects, with vector silencing observed in vitro and in vivo. To overcome this problem, we investigated whether the HS4 chromatin insulator from the chicken beta-globin locus central region could protect a retrovirus vector from position effects. When used to flank a reporter vector, this element significantly increased the fraction of transduced cells that expressed the provirus in cultures and in mice transplanted with transduced marrow. These results demonstrate that a chromatin insulator can improve the expression performance of a widely used class of gene therapy vectors by protecting these vectors from chromosomal position effects.