Genetically engineering cells to perform customizable functions is an emerging frontier with numerous technological and translational applications. However, it remains challenging to systematically engineer mammalian cells to execute complex functions. To address this need, we developed a method enabling accurate genetic program design using high-performing genetic parts and predictive computational models. We built multi-functional proteins integrating both transcriptional and post-translational control, validated models for describing these mechanisms, implemented digital and analog processing, and effectively linked genetic circuits with sensors for multi-input evaluations. The functional modularity and compositional versatility of these parts enable one to satisfy a given design objective via multiple synonymous programs. Our approach empowers bioengineers to predictively design mammalian cellular functions that perform as expected even at high levels of biological complexity.

中文翻译：

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哺乳动物遗传程序的模型指导设计

对细胞进行基因工程以实现可定制功能是具有众多技术和翻译应用的新兴领域。然而，系统工程化哺乳动物细胞以执行复杂功能仍然具有挑战性。为了满足这一需求，我们开发了一种方法，可以使用高性能的遗传部分和预测性计算模型来进行准确的遗传程序设计。我们构建了整合了转录和翻译后控制的多功能蛋白质，用于描述这些机制的经过验证的模型，已实现的数字和模拟处理，以及有效地将遗传电路与传感器连接在一起以进行多输入评估。这些部件的功能模块性和组成上的多功能性使人们可以通过多个同义程序来满足给定的设计目标。