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

Lentiviral vectors containing mouse Csf1r control elements direct macrophage-restricted expression in multiple species of birds and mammals.
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DOI:
10.1038/mtm.2014.10
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发表时间:
2014
期刊:
Molecular therapy. Methods & clinical development
影响因子:
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其他
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巨噬细胞的发育需要通过谱系限制性受体Csf1r进行信号传导。基于Csf1r的转基因报告基因的巨噬细胞限制性表达需要高度保守的Fms-内含子调控元件(FIRE)。我们已经创建了含有小鼠FIRE和启动子的慢病毒构建体。该慢病毒能够指导小鼠、大鼠、人、猪、牛、羊甚至鸡中的巨噬细胞限制性报告基因表达。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。巨噬细胞限制性表达对于免疫或免疫应答调节,以及对于溶酶体贮积病和一些免疫缺陷的基因治疗可能是期望的。Csf1r转录控制元件的小尺寸将允许插入大的"货物",用于基因治疗和疫苗递送。
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.
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