Myeloma xenograft destruction by a nonviral vector delivering oncolytic infectious nucleic acid.
Myeloma xenograft destruction by a nonviral vector delivering oncolytic infectious nucleic acid.
复制标题
通过传递溶瘤感染性核酸的非病毒载体破坏骨髓瘤异种移植物。
DOI：
10.1038/mt.2011.68
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Russell,StephenJ
中科院分区：
文献类型：
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作者：
Hadac,ElizabethM;Kelly,ElizabethJ;Russell,StephenJ
使用非病毒载体制剂启动溶瘤病毒感染的可行性先前尚未得到证实。因此，我们试图确定感染性核酸（INA）是否可以用来代替病毒颗粒启动溶瘤小核糖核酸病毒感染体内。使用T7聚合酶从质粒DNA转录编码柯萨奇病毒A21（CVA 21）的感染性RNA。在将该RNA注射到KAS 6/1骨髓瘤异种移植物中的48小时内，在血流中检测到高滴度的感染性CVA 21病毒体。此后肿瘤迅速消退，小鼠出现肌炎体征。在安乐死时，从消退的肿瘤和骨骼肌中回收CVA 21。瘤内注射裸RNA或完全感染性CVA 21病毒后，治疗结果相当。剂量反应研究表明，通过瘤内注射1 µg感染性RNA可以建立有效的溶瘤感染。溶瘤感染也可以通过静脉注射感染性RNA来启动。我们的研究表明，INA是一个非常有前途的替代药物制剂溶瘤病毒治疗。
The feasibility of using a nonviral vector formulation to initiate an oncolytic viral infection has not been previously demonstrated. We therefore sought to determine whether infectious nucleic acid (INA) could be used in place of virus particles to initiate an oncolytic picornavirus infectionin vivo. Infectious RNA encoding coxsackievirus A21 (CVA21) was transcribed from plasmid DNA using T7 polymerase. Within 48 hours of injecting this RNA into KAS6/1 myeloma xenografts, high titers of infectious CVA21 virions were detected in the bloodstream. Tumors regressed rapidly thereafter and mice developed signs of myositis. At euthanasia, CVA21 was recovered from regressing tumors and from skeletal muscles. Treatment outcomes were comparable following intratumoral injection of naked RNA or fully infectious CVA21 virus. Dose–response studies showed that an effective oncolytic infection could be established by intratumoral injection of 1 µg of infectious RNA. The oncolytic infection could also be initiated by intravenous injection of infectious RNA. Our study demonstrates that INA is a highly promising alternative drug formulation for oncolytic virotherapy.