Corn rootworm-active RNA DvSnf7: Repeat dose oral toxicology assessment in support of human and mammalian safety
Corn rootworm-active RNA DvSnf7: Repeat dose oral toxicology assessment in support of human and mammalian safety
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DOI：
10.1016/j.yrtph.2016.07.009
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发表时间：
2016-11-01
影响因子：
3.4
通讯作者：
Koch, Michael S.
中科院分区：
文献类型：
--
作者：
Petrick, Jay S.;Frierdich, Gregory E.;Koch, Michael S.
转基因作物已经被开发和商业化，它利用双链RNA(DsRNA)来抑制目标基因(S)，产生抗病、营养和品质性状。MON 87411是一个转基因玉米品种，它利用dsRNA选择性地控制玉米根虫，方法是产生一个240bp的dsRNA片段，目的是抑制西部玉米根虫(Diabrotica Virgifera Virgifera)Snf7基因(DvSnf7)。一项生物信息学评估发现，内源玉米小RNA与450至2300个独特的RNA转录本匹配，这些转录本可能编码大鼠、小鼠和人类的蛋白质，表明哺乳动物安全地消费dsRNA。在28天的重复剂量毒性研究中，小鼠以1、10或100 mg/kg的剂量经口给予DvSnf7 RNA(968个核苷酸，包括240个核苷酸的DvSnf7 dsRNA)。在体重、食物摄入量、临床观察、临床化学、血液学、大体病理学或组织病理学终点方面没有观察到与治疗相关的影响。因此，DvSnf7 RNA的未观察到不良反应水平(NOAEL)为100 mg/kg，为所测试的最高剂量。这些结果表明，当口服剂量比预期的人类暴露剂量高出数百万到数十亿倍时，用于昆虫控制的dsRNA不会对哺乳动物产生不良健康影响，因此对哺乳动物的风险可以忽略不计。(C)2016年孟山都公司。由Elsevier Inc.出版。这是CC许可下的一篇开放获取文章。
Genetically modified (GM) crops have been developed and commercialized that utilize double stranded RNAs (dsRNA) to suppress a target gene(s), producing virus resistance, nutritional and quality traits. MON 87411 is a GM maize variety that leverages dsRNAs to selectively control corn rootworm through production of a 240 base pair (bp) dsRNA fragment targeting for suppression the western corn rootworm (Diabrotica virgifera virgifera) Snf7 gene (DvSnf7). A bioinformatics assessment found that endogenous corn small RNAs matched similar to 450 to 2300 unique RNA transcripts that likely code for proteins in rat, mouse, and human, demonstrating safe dsRNA consumption by mammals. Mice were administered DvSnf7 RNA (968 nucleotides, including the 240 bp DvSnf7 dsRNA) at 1, 10, or 100 mg/kg by oral gavage in a 28-day repeat dose toxicity study. No treatment-related effects were observed in body weights, food consumption, clinical observations, clinical chemistry, hematology, gross pathology, or histopathology endpoints. Therefore, the No Observed Adverse Effect Level (NOAEL) for DvSnf7 RNA was 100 mg/kg, the highest dose tested. These results demonstrate that dsRNA for insect control does not produce adverse health effects in mammals at oral doses millions to billions of times higher than anticipated human exposures and therefore poses negligible risk to mammals. (C) 2016 Monsanto Company. Published by Elsevier Inc. This is an open access article under the CC BY license.