Risk assessment of homologous variants of biotech trait proteins using a bridging approach.

IF 4.5 2区农林科学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Gm Crops & Food-Biotechnology in Agriculture and the Food Chain Pub Date : 2024-12-31 Epub Date: 2024-11-09 DOI:10.1080/21645698.2024.2420412

Cunxi Wang, Jennifer Calcaterra, Beverly Anderson, Timothy Rydel, Rong Wang, Lieselot Bertho, Scott A Saracco, Kimberly Hodge-Bell, Luis Burzio, Tommi White, Bin Li

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引用次数: 0

Abstract

A transgenic protein is frequently expressed as different homologous variants in genetically modified crops due to differential processing of targeting peptides or optimization of activity and specificity. The aim of this study was to develop a science-based approach for risk assessment of homologous protein variants using dicamba mono-oxygenase (DMO) as a case study. In this study, DMO expressed in the next-generation dicamba-tolerant maize, sugar beet and soybean crops exhibited up to 27 amino acid sequence differences in the N-terminus. Structure modeling using AlphaFold, ESMFold and OpenFold demonstrates that these small N-terminal extensions lack an ordered secondary structure and do not disrupt the DMO functional structure. Three DMO variants were demonstrated to have equivalent immunoreactivity and functional activity ranging from 214 to 331 nmol/min/mg. Repeated toxicity studies using each DMO variant found no test substance-related adverse effects. These results support that homologous protein variants, which have demonstrated physicochemical and functional equivalence, can leverage existing safety data from one variant without requiring additional de novo safety assessments.

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采用桥接法对生物技术性状蛋白的同源变体进行风险评估。

在转基因作物中，由于靶向肽的不同加工或活性和特异性的优化，转基因蛋白质经常表现为不同的同源变体。本研究的目的是以麦草畏单氧化酶（DMO）为案例，开发一种基于科学的同源蛋白变体风险评估方法。在这项研究中，在耐麦草畏的下一代玉米、甜菜和大豆作物中表达的 DMO 在 N 端表现出多达 27 个氨基酸序列差异。使用 AlphaFold、ESMFold 和 OpenFold 进行的结构建模表明，这些小的 N 端延伸缺乏有序的二级结构，不会破坏 DMO 的功能结构。研究证明，三种 DMO 变体具有同等的免疫活性和功能活性，范围在 214 至 331 nmol/min/mg 之间。使用每种 DMO 变体进行的重复毒性研究均未发现与试验物质相关的不良反应。这些结果证明，已证明理化和功能等效的同源蛋白质变体可以利用一种变体的现有安全性数据，而无需进行额外的全新安全性评估。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Gm Crops & Food-Biotechnology in Agriculture and the Food Chain Biochemistry, Genetics and Molecular Biology-Biotechnology

CiteScore

8.10

自引率

10.30%

发文量

期刊介绍： GM Crops & Food - Biotechnology in Agriculture and the Food Chain aims to publish high quality research papers, reviews, and commentaries on a wide range of topics involving genetically modified (GM) crops in agriculture and genetically modified food. The journal provides a platform for research papers addressing fundamental questions in the development, testing, and application of transgenic crops. The journal further covers topics relating to socio-economic issues, commercialization, trade and societal issues. GM Crops & Food aims to provide an international forum on all issues related to GM crops, especially toward meaningful communication between scientists and policy-makers. GM Crops & Food will publish relevant and high-impact original research with a special focus on novelty-driven studies with the potential for application. The journal also publishes authoritative review articles on current research and policy initiatives, and commentary on broad perspectives regarding genetically modified crops. The journal serves a wide readership including scientists, breeders, and policy-makers, as well as a wider community of readers (educators, policy makers, scholars, science writers and students) interested in agriculture, medicine, biotechnology, investment, and technology transfer. Topics covered include, but are not limited to: • Production and analysis of transgenic crops • Gene insertion studies • Gene silencing • Factors affecting gene expression • Post-translational analysis • Molecular farming • Field trial analysis • Commercialization of modified crops • Safety and regulatory affairs BIOLOGICAL SCIENCE AND TECHNOLOGY • Biofuels • Data from field trials • Development of transformation technology • Elimination of pollutants (Bioremediation) • Gene silencing mechanisms • Genome Editing • Herbicide resistance • Molecular farming • Pest resistance • Plant reproduction (e.g., male sterility, hybrid breeding, apomixis) • Plants with altered composition • Tolerance to abiotic stress • Transgenesis in agriculture • Biofortification and nutrients improvement • Genomic, proteomic and bioinformatics methods used for developing GM cops ECONOMIC, POLITICAL AND SOCIAL ISSUES • Commercialization • Consumer attitudes • International bodies • National and local government policies • Public perception, intellectual property, education, (bio)ethical issues • Regulation, environmental impact and containment • Socio-economic impact • Food safety and security • Risk assessments