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在哺乳动物细胞中的蛋白质分泌的紧可编程控制

Alexander E Vlahos¹, Connor C Call¹, Samarth E Kadaba¹

¹Department of Chemical Engineering, Stanford University, Stanford, CA, 94305, USA.

bioRxiv : the preprint server for biology

|October 24, 2023

概括

合成生物学进步了 Compact RELEASE (compRELEASE),这是一个基于蛋白质的系统,用于精确控制细胞间信号. 这个平台通过使复杂的细胞行为能够实现,并将遗传有效载荷降到最低,从而增强治疗应用.

科学领域:

合成生物学合成生物学
生物医学工程生物医学工程
分子编程是一种分子编程.

背景情况:

基于蛋白质的电路在生物医学中对控制细胞间信号的基因电路具有优势.
像RELEASE这样的先前平台启用了蛋白质酶控制的蛋白质分泌,但缺乏复杂的表达配置,需要多个蛋白质酶.
限制包括交付选项和治疗应用程序的编程复杂性.

研究的目的:

开发一个改进的系统来编程复杂的蛋白质表达特征和控制细胞间信号传输.
为了设计一种工具,尽量减少治疗应用的遗传有效载荷.
为生物医学中先进的合成生物学应用建立一个多功能平台.

主要方法:

利用内源14-3-3蛋白质产生RELEASE-NOT,以抑制蛋白质分泌以应对蛋白酶活性.
结合RELEASE和RELEASE-NOT,形成Compact RELEASE (compRELEASE),是一套蛋白质级处理和输出模块.
利用多基斯特龙单体转录和mRNA输送用于细胞特异性蛋白质表达和分泌控制.

主要成果:

开发了comprELEASE,可以通过单个输入蛋白酶进行逻辑处理和模拟信号过.
通过lentiviral集成和mRNA传递来控制蛋白质分泌的经过翻译后紧的设计.
通过可诱导蛋白酶在工程细胞中实现细胞表面蛋白的选择性表达.

结论:

compRELEASE显著提高了合成蛋白质电路在治疗应用中的潜力.
该系统允许对蛋白质分泌进行复杂的控制,并尽量减少遗传有效载荷.
这一进步为生物医学提供了复杂的细胞工程.

关键词:

14-3-3 蛋白质的使用情况细胞间通信是细胞间的通信.提供mRNA的交付.蛋白质酶是一种蛋白质酶.蛋白质的电路是蛋白质的电路.合成生物学合成生物学

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