Phenotype correction of Fanconi anemia group A hematopoietic stem cells using lentiviral vector.
Phenotype correction of Fanconi anemia group A hematopoietic stem cells using lentiviral vector.
复制标题
使用慢病毒载体对范可尼贫血 A 组造血干细胞进行表型校正。
DOI：
10.1016/s1525-0016(03)00223-5
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Walsh,ChristopherE
中科院分区：
文献类型：
--
作者：
Yamada,Kaoru;Ramezani,Ali;Hawley,RobertG;Ebell,Wolfram;Arwert,Fre;Arnold,LarryW;Walsh,ChristopherE
Fanconi anemia (FA) is an autosomal recessive disease characterized by progressive bone marrow failure due to defective stem cell function. FA patients' cells are hypersensitive to DNA cross-linking agents such as mitomycin C (MMC), exposure to which results in cytogenetic aberrations and cell death. To date Moloney murine leukemia virus vectors have been used in clinical gene therapy. Recently, third-generation lentiviral vectors based on the HIV-1 genome have been developed for efficient gene transfer to hematopoietic stem cells. We generated a self-inactivating lentiviral vector expressing the FA group A cDNA driven by the murine stem cell virus U3 LTR promoter and used the vector to transduce side-population (SP) cells isolated from bone marrow of Fanconi anemia group A (Fanca) knockout mice. One thousand transduced SP cells reconstituted the bone marrow of sublethally irradiated Fanca recipient mice. Phenotype correction was demonstrated by stable hematopoiesis following MMC challenge. Using real-time PCR, one proviral vector DNA copy per cell was detected in all lineage-committed cells in the peripheral blood of both primary and secondary recipients. Our results suggest that the lentiviral vector transduces stem cells capable of self-renewal and long-term hematopoiesisin vivoand is potentially useful for clinical gene therapy of FA hematopoietic cells.
