Specific gene transfer to neurons, endothelial cells and hematopoietic progenitors with lentiviral vectors
Specific gene transfer to neurons, endothelial cells and hematopoietic progenitors with lentiviral vectors
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DOI：
10.1038/nmeth.1514
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发表时间：
2010-11-01
期刊：
影响因子：
48
通讯作者：
Buchholz, Christian J.
中科院分区：
文献类型：
--
作者：
Anliker, Brigitte;Abel, Tobias;Buchholz, Christian J.
我们提出了一个灵活的和高度特异性的慢病毒载体的基础上识别细胞表面抗原的单链抗体的靶向方法。我们制备了对人CD 105（+）内皮细胞、人CD 133（+）造血祖细胞和小鼠GluA表达神经元特异性的慢病毒载体。对CD 105或CD 20特异性的慢病毒载体与VSV-G假型载体一样有效地转导其靶细胞，但在混合培养物中区分内皮细胞和淋巴细胞。CD 133靶向载体转导CD 133（+）培养的造血祖细胞比VSV-G假型载体更有效，导致稳定的长期转导。靶向谷氨酸受体亚基GluA 2和GluA 4的慢病毒载体对小脑培养物中的神经元和注射到成年小鼠脑中时表现出超过94%的特异性。我们观察到的Cre重组酶基因转移到报告小鼠的海马神经元特异性基因修饰。这种方法允许靶向基因转移到许多感兴趣的细胞类型，具有前所未有的特异性。
We present a flexible and highly specific targeting method for lentiviral vectors based on single-chain antibodies recognizing cell-surface antigens. We generated lentiviral vectors specific for human CD105(+) endothelial cells, human CD133(+) hematopoietic progenitors and mouse GluA-expressing neurons. Lentiviral vectors specific for CD105 or for CD20 transduced their target cells as efficiently as VSV-G pseudotyped vectors but discriminated between endothelial cells and lymphocytes in mixed cultures. CD133-targeted vectors transduced CD133(+) cultured hematopoietic progenitor cells more efficiently than VSV-G pseudotyped vectors, resulting in stable long-term transduction. Lentiviral vectors targeted to the glutamate receptor subunits GluA2 and GluA4 exhibited more than 94% specificity for neurons in cerebellar cultures and when injected into the adult mouse brain. We observed neuron-specific gene modification upon transfer of the Cre recombinase gene into the hippocampus of reporter mice. This approach allowed targeted gene transfer to many cell types of interest with an unprecedented degree of specificity.