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利用纤维修饰的重组腺病毒向人造血细胞中高效传递白细胞介素 2 基因

An Efficient Method for the Delivery of the Interleukin-2 Gene to Human Hematopoietic Cells using the 
Fiber-Modified Recombinant Adenovirus.

机构信息

Gamaleya Research Institute of Epidemiology and Microbiology, Ministry of Health and Social Development of the Russian Federation.

出版信息

Acta Naturae. 2011 Jul;3(3):100-6.

PMID:22649700
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3347609/
Abstract

Recombinant human adenovirus serotype 5 (Ad5/35F-IL2) with modified fibres containing the C-terminal domain fiber-knob of human adenovirus serotype 35, carrying the gene of recombinant human IL-2, has been designed. As a result of the fiber modification, the adenovirus can efficiently deliver the genetic information to bone marrow leukocytes and the tumor blood cells KG-1A (human myeloblastic leukemia cells) and U937 (human histiocytic lymphoma cells), which are normally resistant to Ad5 infection. The flow cytometry data reveal that the modified Ad5/35F penetrates into a population of monocytes, granulocytes, and blast cells of human bone marrow. The expression of interleukin-2 in CAR-negative bone marrow leukocytes (3682.52 ± 134.21 pg/ml) and the cell lines KG-1A (748.3 ± 32.8 pg/ml) and U937 (421.5 ± 59.4 pg/ml) transduced with adenovirus Ad5/35F-IL2 is demonstrated. The fiber-modified adenovirus can be used as a vector for the efficient gene delivery of interleukin-2 to human normal and tumor hematopoietic cells.

摘要

设计了一种携带重组人白细胞介素 2 基因的纤维末端结构域经改造的人 5 型腺病毒（Ad5/35F-IL2），其纤维末端结构域经改造后可以高效地将遗传信息递送至骨髓白细胞、肿瘤细胞系 KG-1A（人髓性白血病细胞）和 U937（人组织细胞淋巴瘤细胞）。这些肿瘤细胞通常对 Ad5 感染具有抗性。流式细胞术数据表明，改造后的 Ad5/35F 能够穿透入人群中的单核细胞、粒细胞和骨髓原始细胞。经改造的腺病毒 Ad5/35F-IL2 转导的 CAR-阴性骨髓白细胞（3682.52 ± 134.21 pg/ml）、KG-1A（748.3 ± 32.8 pg/ml）和 U937（421.5 ± 59.4 pg/ml）中均有白细胞介素 2 的表达。纤维末端结构域经改造的腺病毒可以作为人正常和肿瘤造血细胞高效白细胞介素 2 基因递送的载体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/febf/3347609/30a2f56ed44c/AN20758251-10-100-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/febf/3347609/da331bb787cf/AN20758251-10-100-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/febf/3347609/f042793341d8/AN20758251-10-100-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/febf/3347609/162d70a3d9d8/AN20758251-10-100-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/febf/3347609/d24d31296cae/AN20758251-10-100-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/febf/3347609/a784c2a9b004/AN20758251-10-100-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/febf/3347609/30a2f56ed44c/AN20758251-10-100-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/febf/3347609/da331bb787cf/AN20758251-10-100-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/febf/3347609/0c72d4d12a9e/AN20758251-10-100-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/febf/3347609/79c5db05b4e4/AN20758251-10-100-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/febf/3347609/f042793341d8/AN20758251-10-100-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/febf/3347609/162d70a3d9d8/AN20758251-10-100-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/febf/3347609/d24d31296cae/AN20758251-10-100-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/febf/3347609/a784c2a9b004/AN20758251-10-100-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/febf/3347609/30a2f56ed44c/AN20758251-10-100-g008.jpg

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