Fundamental computer science concepts have inspired novel information-processing molecular systems in test tubes^{1,2,3,4,5,6,7,8,9,10,11,12,13} and genetically encoded circuits in live cells^{14,15,16,17,18,19,20,21}. Recent research has shown that digital information storage in DNA, implemented using deep sequencing and conventional software, can approach the maximum Shannon information capacity²² of two bits per nucleotide²³. In nature, DNA is used to store genetic programs, but the information content of the encoding rarely approaches this maximum²⁴. We hypothesize that the biological function of a genetic program can be preserved while reducing the length of its DNA encoding and increasing the information content per nucleotide. Here we support this hypothesis by describing an experimental procedure for compressing a genetic program and its subsequent autonomous decompression and execution in human cells. As a test-bed we choose an RNAi cell classifier circuit²⁵ that comprises redundant DNA sequences and is therefore amenable for compression, as are many other complex gene circuits^{15,18,26,27,28}. In one example, we implement a compressed encoding of a ten-gene four-input AND gate circuit using only four genetic constructs. The compression principles applied to gene circuits can enable fitting complex genetic programs into DNA delivery vehicles with limited cargo capacity, and storing compressed and biologically inert programs in vivo for on-demand activation.

中文翻译：

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遗传程序可以在活细胞中压缩和自主解压

基本的计算机科学概念激发了试管中新型信息处理分子系统^{1,2,3,4,5,6,7,8,9,10,11,12,13}和活细胞中的基因编码电路^{14,15 ,16,17,18,19,20,21} . 最近的研究表明，使用深度测序和常规软件实现的 DNA 中的数字信息存储可以接近每个核苷酸两位的最大香农信息容量^{22 23}。在自然界中，DNA 用于存储遗传程序，但编码的信息内容很少接近这个最大值²⁴。我们假设遗传程序的生物学功能可以被保留，同时减少其 DNA 编码的长度并增加每个核苷酸的信息内容。在这里，我们通过描述压缩遗传程序及其随后在人体细胞中自主解压和执行的实验程序来支持这一假设。作为测试平台，我们选择包含冗余DNA序列的RNAi细胞分类器电路²⁵，因此适合压缩，许多其他复杂基因电路^{15,18,26,27,28}也是如此。在一个示例中，我们仅使用四个遗传结构实现了十基因四输入与门电路的压缩编码。应用于基因电路的压缩原理可以将复杂的遗传程序安装到载重量有限的DNA递送载体中，并在体内存储压缩的和生物惰性的程序以供按需激活。