IFN-beta gene transfer into the central nervous system using bone marrow cells as a delivery system.
IFN-beta gene transfer into the central nervous system using bone marrow cells as a delivery system.
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使用骨髓细胞作为传递系统将 IFN-β 基因转移到中枢神经系统。
DOI：
10.1089/107999002320271378
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Dhib-Jalbut,Suhayl
中科院分区：
文献类型：
--
作者：
Makar,TapasKumar;Wilt,Susan;Dong,Zhongyun;Fishman,Paul;Mouradian,MMaral;Dhib-Jalbut,Suhayl
由于血脑屏障的存在，干扰素-β(干扰素-β)外周给药治疗中枢神经系统疾病仅有部分疗效。为了避免这个问题，我们评估了通过基因改变骨髓细胞性活体并将其作为载体将干扰素-β基因转移到小鼠中枢神经系统的可行性。用干扰素β逆转录病毒表达载体(pLXSN-干扰素β)稳定转染PA317细胞。用表达干扰素-β基因和蛋白的分泌细胞上清液感染骨髓细胞。当移植到受照射的小鼠体内时，干扰素-β工程的骨髓细胞进入中枢神经系统，并表达干扰素-β的基因和蛋白。用对照新霉素载体转导的骨髓细胞进入大脑，表达新霉素，但不表达干扰素-β基因。在中枢神经系统中，骨髓细胞递送的干扰素-β诱导2‘，5’-寡腺苷合成酶(2‘，5’-OAS)的基因表达，表明其具有生物学活性。我们的研究结果表明，骨髓细胞可以作为干扰素-β基因进入中枢神经系统的输送系统，这可能对多发性硬化症(MS)、病毒性脑炎和脑肿瘤等神经系统疾病的治疗具有指导意义。
The peripheral delivery of interferon-β(IFN-β) for the treatment of central nervous system (CNS) diseases is only partially effective because of the blood-brain barrier (BBB). To circumvent this problem, we evaluated the feasibility of genetically altering bone marrow cellsex vivoand using them as vehicles to transfer the IFN-βcDNA into the mouse CNS. An IFN-βretroviral expression vector (pLXSN-IFNβ) was used to stably transfect PA317 cells. The supernatant from these producer cells, which expressed IFN-βmRNA and protein, were used to infect bone marrow cells. When transplanted into irradiated mice, IFN-β-engineered marrow cells accessed the CNS and expressed IFN-βmRNA and protein. Marrow cells transduced with a control neomycin vector entered the brain and expressed the neomycin but not the IFN-βgene. In the CNS, IFN-βdelivered by marrow cells induced the mRNA expression of 2′,5′-oligoadenylate synthetase (2′,5′-OAS), indicating biologic activity. Our findings demonstrating that bone marrow cells can serve as a delivery system for IFN-βcDNA into the CNS could have implications for the treatment of neurologic disorders, such as multiple sclerosis (MS), viral encephalitis, and brain tumors.