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History of safe exposure and bioinformatic assessment of phosphomannose-isomerase (PMI) for allergenic risk
Transgenic Research ( IF 3 ) Pub Date : 2021-03-24 , DOI: 10.1007/s11248-021-00243-0
Rod A Herman 1 , Zhenglin Hou 2 , Henry Mirsky 2 , Mark E Nelson 2 , Carey A Mathesius 2 , Jason M Roper 3
Affiliation  

Newly expressed proteins in genetically engineered crops are evaluated for potential cross reactivity to known allergens as part of their safety assessment. This assessment uses a weight-of-evidence approach. Two key components of this allergenicity assessment include any history of safe human exposure to the protein and/or the source organism from which it was originally derived, and bioinformatic analysis identifying amino acid sequence relatedness to known allergens. Phosphomannose-isomerase (PMI) has been expressed in commercialized genetically engineered (GE) crops as a selectable marker since 2010 with no known reports of allergy, which supports a history of safe exposure, and GE events expressing the PMI protein have been approved globally based on expert safety analysis. Bioinformatic analyses identified an eight-amino-acid contiguous match between PMI and a frog parvalbumin allergen (CAC83047.1). While short amino acid matches have been shown to be a poor predictor of allergen cross reactivity, most regulatory bodies require such matches be assessed in support of the allergenicity risk assessment. Here, this match is shown to be of negligible risk of conferring cross reactivity with known allergens.



中文翻译:

磷酸甘露糖异构酶 (PMI) 过敏风险的安全暴露史和生物信息学评估

作为其安全性评估的一部分,评估了基因工程作物中新表达的蛋白质与已知过敏原的潜在交叉反应性。该评估使用证据权重方法。这种过敏性评估的两个关键组成部分包括人类安全暴露于蛋白质和/或蛋白质最初来源的生物源的任何历史,以及识别氨基酸序列与已知过敏原相关性的生物信息学分析。自 2010 年以来,磷酸甘露糖异构酶 (PMI) 已在商业化的基因工程 (GE) 作物中作为选择标记表达,没有已知的过敏报告,支持安全暴露的历史,表达 PMI 蛋白的 GE 事件已在全球范围内获得批准关于专家安全分析。生物信息学分析确定了 PMI 和青蛙小清蛋白过敏原 (CAC83047.1) 之间的八氨基酸连续匹配。虽然短氨基酸匹配已被证明是过敏原交叉反应性的不良预测指标,但大多数监管机构要求评估此类匹配以支持过敏风险评估。在这里,这种匹配显示出与已知过敏原交叉反应的风险可以忽略不计。

更新日期:2021-03-24
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