کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9283026 | 1224999 | 2005 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
HIV-1-derived self-inactivating lentivirus vector induces megakaryocyte lineage-specific gene expression
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ایمونولوژی
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![عکس صفحه اول مقاله: HIV-1-derived self-inactivating lentivirus vector induces megakaryocyte lineage-specific gene expression HIV-1-derived self-inactivating lentivirus vector induces megakaryocyte lineage-specific gene expression](/preview/png/9283026.png)
چکیده انگلیسی
Pluripotent, self-renewing, hematopoietic stem cells are considered good targets for gene modification to treat a wide variety of disorders. However, as many genes are expressed in a stage-specific manner during the course of hematopoietic development, it is necessary to establish a lineage-specific gene expression system to ensure the proper expression of transduced genes in hematopoietic stem cells. In this study, we constructed a VSV-G-pseudotyped, human immunodeficiency virus type 1-based, self-inactivating lentivirus vector that expressed green fluorescent protein (GFP) under the control of the human CD41 (glycoprotein 2b; GP2b) promoter; this activity is restricted to megakaryocytic lineage cells. The recombinant virus was used to infect human peripheral blood CD34+ (hematopoietic stem/progenitor) cells, and lineage-specific gene expression was monitored with GFP measurements. The analysis by FACS determined that GFP expression driven by the GP2b promoter was restricted to megakaryocytic progenitors and was not present in erythrocytes. Furthermore, in the hematopoietic colony-forming assay, GFP expression was restricted to colony-forming units-megakaryocyte (CFU-Meg) colonies under the control of the GP2b promoter, whereas all myeloid colonies (burst-forming units-erythroid, colony-forming units-granulocyte-macrophage, and CFU-Meg) expressed GFP when the transgene was regulated by the cytomegalovirus promoter. These results demonstrated lineage-specific expression after gene transduction of hematopoietic stem cells. The application of this vector system should provide a useful tool for gene therapy to treat disorders associated with megakaryocyte (platelet) dysfunction.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Microbes and Infection - Volume 7, Issue 2, February 2005, Pages 240-247
Journal: Microbes and Infection - Volume 7, Issue 2, February 2005, Pages 240-247
نویسندگان
Kazuta Yasui, Rika A. Furuta, Kayoko Matsumoto, Yoshihiko Tani, Jun-ichi Fujisawa,