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携带小鼠 Csf1r 控制元件的慢病毒载体可在多种鸟类和哺乳动物中指导巨噬细胞特异性表达。

Lentiviral vectors containing mouse Csf1r control elements direct macrophage-restricted expression in multiple species of birds and mammals.

机构信息

The Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Scotland , UK.

出版信息

Mol Ther Methods Clin Dev. 2014 Apr 9;1:14010. doi: 10.1038/mtm.2014.10. eCollection 2014.

Abstract

The development of macrophages requires signaling through the lineage-restricted receptor Csf1r. Macrophage-restricted expression of transgenic reporters based upon Csf1r requires the highly conserved Fms-intronic regulatory element (FIRE). We have created a lentiviral construct containing mouse FIRE and promoter. The lentivirus is capable of directing macrophage-restricted reporter gene expression in mouse, rat, human, pig, cow, sheep, and even chicken. Rat bone marrow cells transduced with the lentivirus were capable of differentiating into macrophages expressing the reporter gene in vitro. Macrophage-restricted expression may be desirable for immunization or immune response modulation, and for gene therapy for lysosomal storage diseases and some immunodeficiencies. The small size of the Csf1r transcription control elements will allow the insertion of large "cargo" for applications in gene therapy and vaccine delivery.

摘要

巨噬细胞的发育需要通过谱系特异性受体 Csf1r 进行信号转导。基于 Csf1r 的转基因报告基因在巨噬细胞中的特异性表达需要高度保守的 Fms 内含子调控元件(FIRE)。我们构建了一个包含小鼠 FIRE 和启动子的慢病毒载体。该慢病毒能够在小鼠、大鼠、人类、猪、牛、绵羊,甚至鸡中指导巨噬细胞特异性报告基因的表达。用慢病毒转导的大鼠骨髓细胞能够在体外分化为表达报告基因的巨噬细胞。巨噬细胞特异性表达可能是免疫接种或免疫反应调节以及溶酶体贮积病和某些免疫缺陷的基因治疗所需要的。Csf1r 转录调控元件的小尺寸将允许插入大的“货物”,用于基因治疗和疫苗传递应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8268/4362345/fb65deb1b4b6/mtm201410-f1.jpg

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