Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 116, Issue 15, Pages 7214-7219Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1821740116
Keywords
synthetic biology; biocomputing; genetic engineering
Categories
Funding
- European Research Council advanced Grant (ProNet) [321381]
- National Centre of Competence in Research for Molecular Systems Engineering
- European Research Council (ERC) [321381] Funding Source: European Research Council (ERC)
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Controlling gene expression with sophisticated logic gates has been and remains one of the central aims of synthetic biology. However, conventional implementations of biocomputers use central processing units (CPUs) assembled from multiple protein-based gene switches, limiting the programming flexibility and complexity that can be achieved within single cells. Here, we introduce a CRISPR/Cas9-based core processor that enables different sets of user-defined guide RNA inputs to program a single transcriptional regulator (dCas9-KRAB) to perform a wide range of bitwise computations, from simple Boolean logic gates to arithmetic operations such as the half adder. Furthermore, we built a dual-core CPU combining two orthogonal core processors in a single cell. In principle, human cells integrating multiple orthogonal CRISPR/Cas9-based core processors could offer enormous computational capacity.
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