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Evaluating the probability of CRISPR-based gene drive contaminating another species.
Evolutionary Applications ( IF 4.1 ) Pub Date : 2020-04-17 , DOI: 10.1111/eva.12939
Virginie Courtier-Orgogozo 1 , Antoine Danchin 2 , Pierre-Henri Gouyon 3 , Christophe Boëte 4
Affiliation  

The probability D that a given clustered regularly interspaced short palindromic repeats (CRISPR)‐based gene drive element contaminates another, nontarget species can be estimated by the following Drive Risk Assessment Quantitative Estimate (DRAQUE) Equation: urn:x-wiley:17524571:media:eva12939:eva12939-math-0001 with hyb = probability of hybridization between the target species and a nontarget species; transf = probability of horizontal transfer of a piece of DNA containing the gene drive cassette from the target species to a nontarget species (with no hybridization); express = probability that the Cas9 and guide RNA genes are expressed; cut = probability that the CRISPR‐guide RNA recognizes and cuts at a DNA site in the new host; flank = probability that the gene drive cassette inserts at the cut site; immune = probability that the immune system does not reject Cas9‐expressing cells; nonextinct = probability of invasion of the drive within the population. We discuss and estimate each of the seven parameters of the equation, with particular emphasis on possible transfers within insects, and between rodents and humans. We conclude from current data that the probability of a gene drive cassette to contaminate another species is not insignificant. We propose strategies to reduce this risk and call for more work on estimating all the parameters of the formula.

中文翻译:

评估基于 CRISPR 的基因驱动污染另一个物种的可能性。

给定的基于簇的规则间隔短回文重复序列 (CRISPR) 的基因驱动元件污染另一个非目标物种的概率 D 可以通过以下驱动风险评估定量估计 (DRAQUE) 方程进行估计:其中瓮:x-wiley:17524571:媒体:eva12939:eva12939-math-0001hyb = 目标之间杂交的概率物种和非目标物种;transf  = 含有基因驱动盒的 DNA 片段从目标物种水平转移到非目标物种的概率(无杂交);express  = Cas9和指导RNA基因表达的概率;cut  = CRISPR-guide RNA 在新宿主中识别并切割 DNA 位点的概率;flank  = 基因驱动盒插入切割位点的概率;免疫 = 免疫系统不排斥Cas9表达细胞的概率;非灭绝 = 驱动器入侵种群内的概率。我们讨论并估计了方程的七个参数中的每一个,特别强调昆虫体内以及啮齿动物和人类之间可能的转移。我们从当前数据得出结论,基因驱动盒污染另一个物种的可能性并非微不足道。我们提出了降低这种风险的策略,并呼吁开展更多工作来估计公式的所有参数。
更新日期:2020-04-17
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