Design of HIV vectors for efficient gene delivery into human hematopoietic cells

Design of HIV vectors for efficient gene delivery into human hematopoietic cells
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DOI:
10.1006/mthe.2002.0558
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发表时间:
2002-04-01
期刊:
影响因子:
12.4
通讯作者:
Yee, JK
Yee, JK
中科院分区:
医学1区
文献类型:
--
作者:
Yam, PY;Li, SL;Yee, JK

文献摘要

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来自人类免疫缺陷病毒(HIV)的载体有望有效地将基因输送到人类造血细胞。本研究使用含有不同顺式作用元件组合的HIV载体,包括HIV中央翻盖序列和土拨鼠转录后调控元件(WPRE),并结合两种不同的启动子,转导原代人类淋巴细胞和脐血CD34+祖细胞。系统评价了这些因素对转基因效率和转基因表达的影响。结果表明,利用FLOW、WPRE序列和来自脾肿瘤形成病毒(SFFV)的启动子的组合,外源基因可以有效地导入原代人T淋巴细胞和脐带血CD34+细胞。这项研究为适当的载体设计建立了参数,以有效地将外源基因输送到人类造血细胞中。
Vectors derived from human immunodeficiency virus (HIV) hold promise for efficient gene delivery into human hematopoietic cells. In this study, HIV vectors containing different combinations of cis-acting elements, including the HIV central flap sequence, and the woodchuck postranscriptional regulatory element (WPRE) in combination with two different promoters, were used to transduce primary human lymphocytes and cord blood CD34+ progenitor cells. The effect of these elements on the transduction efficiency and transgene expression was systematically evaluated. The results demonstrate that with the combination of flap, WPRE sequences, and the promoter derived from spleen focus-forming virus (SFFV), a foreign gene can be efficiently delivered into primary human T lymphocytes and cord blood CD34+ cells. The study establishes the parameters for proper vector design to efficiently deliver foreign genes into human hematopoietic cells.