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首页> 外文期刊>Nature nanotechnology >Genetic programs can be compressed and autonomously decompressed in live cells
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Genetic programs can be compressed and autonomously decompressed in live cells

机译:遗传程序可以在活细胞中压缩和自主地减压

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摘要

Fundamental computer science concepts have inspired novel information-processing molecular systems in test tubes(1)(-13) and genetically encoded circuits in live cells(14)(-21). Recent research has shown that digital information storage in DNA, implemented using deep sequencing and conventional software, can approach the maximum Shannon information capacity(22) of two bits per nucleotide(23). In nature, DNA is used to store genetic programs, but the information content of the encoding rarely approaches this maximum(24). 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 circuit(25) that comprises redundant DNA sequences and is therefore amenable for compression , as are many other complex gene circuits(15)(,18,26-28). 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.
机译:基础计算机科学概念在活细胞(14)(14)( - 21)中的基因编码电路和遗传编码电路中的新型信息处理分子系统启发了新的信息处理分子系统。最近的研究表明,DNA中的数字信息存储,使用深度测序和常规软件实现,可以接近每核苷酸(23)的两个比特的最大Shannon信息容量(22)。本质上,DNA用于存储遗传程序,但编码的信息内容很少接近该最大(24)。我们假设可以保留遗传程序的生物学功能,同时降低其DNA编码的长度并增加每核苷酸的信息含量。在这里,我们通过描述用于压缩遗传计划的实验程序及其随后的自主减压和在人体细胞中执行的实验程序来支持这一假设。作为试验床,我们选择一个RNAi细胞分类器电路(25),其包括冗余DNA序列,因此适用于压缩,也可以是许多其他复杂基因电路(15)(,18,26-28)。在一个示例中,我们仅使用四个遗传构建体实现十个基因四输入和栅极电路的压缩编码。应用于基因电路的压缩原理可以使复杂的遗传程序拟合到具有有限的货物能力的DNA递送车辆中,并在体内存储压缩和生物惰性程序以进行按需激活。

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