A revolutionary tool: CRISPR technology plays an important role in construction of intelligentized gene circuits

With the development of synthetic biology, synthetic gene circuits have shown great applied potential in medicine, biology, and as commodity chemicals. An ultimate challenge in the construction of gene circuits is the lack of effective, programmable, secure and sequence‐specific gene editing tools. The clustered regularly interspaced short palindromic repeat (CRISPR) system, a CRISPR‐associated RNA‐guided endonuclease Cas9 (CRISPR‐associated protein 9)‐targeted genome editing tool, has recently been applied in engineering gene circuits for its unique properties‐operability, high efficiency and programmability. The traditional single‐targeted therapy cannot effectively distinguish tumour cells from normal cells, and gene therapy for single targets has poor anti‐tumour effects, which severely limits the application of gene therapy. Currently, the design of gene circuits using tumour‐specific targets based on CRISPR/Cas systems provides a new way for precision cancer therapy. Hence, the application of intelligentized gene circuits based on CRISPR technology effectively guarantees the safety, efficiency and specificity of cancer therapy. Here, we assessed the use of synthetic gene circuits and if the CRISPR system could be used, especially artificial switch‐inducible Cas9, to more effectively target and treat tumour cells. Moreover, we also discussed recent advances, prospectives and underlying challenges in CRISPR‐based gene circuit development.

[1]  J. Keith Joung,et al.  Improving CRISPR-Cas nuclease specificity using truncated guide RNAs , 2014, Nature Biotechnology.

[2]  Hildegard Büning,et al.  Small But Increasingly Mighty: Latest Advances in AAV Vector Research, Design, and Evolution. , 2017, Human gene therapy.

[3]  Yuchen Liu,et al.  Synthesizing artificial devices that redirect cellular information at will , 2018, eLife.

[4]  G. Church,et al.  Cas9 gRNA engineering for genome editing, activation and repression , 2015, Nature Methods.

[5]  Martin Fussenegger,et al.  A closed-loop synthetic gene circuit for the treatment of diet-induced obesity in mice , 2013, Nature Communications.

[6]  Martin Fussenegger,et al.  A designer cell-based histamine-specific human allergy profiler , 2014, Nature Communications.

[7]  Jennifer A. Doudna,et al.  Disabling Cas9 by an anti-CRISPR DNA mimic , 2017, Science Advances.

[8]  Yinqing Li,et al.  Crystal Structure of Staphylococcus aureus Cas9 , 2015, Cell.

[9]  L. Nissim,et al.  Multiplexed and programmable regulation of gene networks with an integrated RNA and CRISPR/Cas toolkit in human cells. , 2014, Molecular cell.

[10]  Christopher A. Voigt,et al.  Principles of genetic circuit design , 2014, Nature Methods.

[11]  Dean Bok,et al.  Complement modulation in the retinal pigment epithelium rescues photoreceptor degeneration in a mouse model of Stargardt disease , 2017, Proceedings of the National Academy of Sciences.

[12]  M. Elowitz,et al.  Synthetic Biology: Integrated Gene Circuits , 2011, Science.

[13]  R. Weiss,et al.  Multi-input Rnai-based Logic Circuit for Identification of Specific , 2022 .

[14]  Moritoshi Sato,et al.  CRISPR-Cas9-based photoactivatable transcription system. , 2015, Chemistry & biology.

[15]  Sita J. Saunders,et al.  An updated evolutionary classification of CRISPR–Cas systems , 2015, Nature Reviews Microbiology.

[16]  Z. Cai,et al.  Synthesizing AND gate genetic circuits based on CRISPR-Cas9 for identification of bladder cancer cells , 2014, Nature Communications.

[17]  J. Keith Joung,et al.  731. High-Fidelity CRISPR-Cas9 Nucleases with No Detectable Genome-Wide Off-Target Effects , 2016 .

[18]  James A Thomson,et al.  Simultaneous reprogramming and gene editing of human fibroblasts , 2018, Nature Protocols.

[19]  Matthew Meyerson,et al.  Targeted genomic rearrangements using CRISPR/Cas technology , 2014, Nature Communications.

[20]  Joana A. Vidigal,et al.  In vivo engineering of oncogenic chromosomal rearrangements with the CRISPR/Cas9 system , 2014, Nature.

[21]  Rainer Breitling,et al.  Orthogonal Regulatory Circuits for Escherichia coli Based on the γ-Butyrolactone System of Streptomyces coelicolor. , 2018, ACS synthetic biology.

[22]  Yarden Katz,et al.  Multiplexed activation of endogenous genes by CRISPR-on, an RNA-guided transcriptional activator system , 2013, Cell Research.

[23]  Rainer Fischer,et al.  CRISPR/Cas9‐mediated knockout of six glycosyltransferase genes in Nicotiana benthamiana for the production of recombinant proteins lacking β‐1,2‐xylose and core α‐1,3‐fucose , 2018, Plant biotechnology journal.

[24]  Jennifer A. Doudna,et al.  DNA interrogation by the CRISPR RNA-guided endonuclease Cas9 , 2014, Nature.

[25]  Jinghong Han,et al.  Engineering cell signaling using tunable CRISPR–Cpf1-based transcription factors , 2017, Nature Communications.

[26]  R. Weiss,et al.  CRISPR transcriptional repression devices and layered circuits in mammalian cells , 2014, Nature Methods.

[27]  Luke A. Gilbert,et al.  Engineering Complex Synthetic Transcriptional Programs with CRISPR RNA Scaffolds , 2015, Cell.

[28]  Prashant Mali,et al.  Orthogonal Cas9 Proteins for RNA-Guided Gene Regulation and Editing , 2013, Nature Methods.

[29]  Michael Z. Lin,et al.  A Single-Chain Photoswitchable CRISPR-Cas9 Architecture for Light-Inducible Gene Editing and Transcription , 2017, ACS chemical biology.

[30]  Molly Megraw,et al.  Small Genetic Circuits and MicroRNAs: Big Players in Polymerase II Transcriptional Control in Plants , 2016, Plant Cell.

[31]  Jennifer A. Doudna,et al.  Enhanced proofreading governs CRISPR-Cas9 targeting accuracy , 2017, Nature.

[32]  Luke A. Gilbert,et al.  Repurposing CRISPR as an RNA-Guided Platform for Sequence-Specific Control of Gene Expression , 2013, Cell.

[33]  L. Nissim,et al.  A tunable dual-promoter integrator for targeting of cancer cells , 2010, Molecular systems biology.

[34]  Justin Schwartz.  Engineering , 1929, Nature.

[35]  Adam P Arkin,et al.  An adaptor from translational to transcriptional control enables predictable assembly of complex regulation , 2012, Nature Methods.

[36]  Jennifer A. Doudna,et al.  A Broad-Spectrum Inhibitor of CRISPR-Cas9 , 2017, Cell.

[37]  Christina D Smolke,et al.  Reprogramming Cellular Behavior with RNA Controllers Responsive to Endogenous Proteins , 2010, Science.

[38]  Lei S Qi,et al.  Engineering cell sensing and responses using a GPCR-coupled CRISPR-Cas system , 2017, Nature Communications.

[39]  Joana A. Vidigal,et al.  Corrigendum: In vivo engineering of oncogenic chromosomal rearrangements with the CRISPR/Cas9 system , 2015, Nature.

[40]  D. Hanahan,et al.  The Hallmarks of Cancer , 2000, Cell.

[41]  Zhen Xie,et al.  Modular construction of mammalian gene circuits using TALE transcriptional repressors , 2014, Nature chemical biology.

[42]  Rahul Sarpeshkar,et al.  Synthetic analog computation in living cells , 2013, Nature.

[43]  J. Doudna,et al.  RNA-guided genetic silencing systems in bacteria and archaea , 2012, Nature.

[44]  Dacheng Ma,et al.  Integration and exchange of split dCas9 domains for transcriptional controls in mammalian cells , 2016, Nature Communications.

[45]  Ron Weiss,et al.  Genetically programmable pathogen sense and destroy. , 2013, ACS synthetic biology.

[46]  Max A. Horlbeck,et al.  Genome-Scale CRISPR-Mediated Control of Gene Repression and Activation , 2014, Cell.

[47]  D. Henning.  Metabolism , 1972, Introduction to a Phenomenology of Life.

[48]  Xiaoqiang Guo,et al.  Directing cellular information flow via CRISPR signal conductors , 2016, Nature Methods.

[49]  Claudia C. Wehrspaun,et al.  Synthetic RNA-Based Immunomodulatory Gene Circuits for Cancer Immunotherapy , 2017, Cell.

[50]  C. Gersbach,et al.  Engineering synthetic TALE and CRISPR/Cas9 transcription factors for regulating gene expression. , 2014, Methods.

[51]  Suk-Young Lee,et al.  Changing strategies for target therapy in gastric cancer. , 2016, World journal of gastroenterology.

[52]  J. Keasling,et al.  Engineering Cellular Metabolism , 2016, Cell.

[53]  Michel Sadelain,et al.  Gene therapy comes of age , 2018, Science.

[54]  Timothy K Lu,et al.  Engineering Synthetic Gene Circuits in Living Cells with CRISPR Technology. , 2016, Trends in biotechnology.

[55]  G. Church,et al.  Synthetic Gene Networks That Count , 2009, Science.

[56]  David Z. Chen,et al.  Architecture of the human regulatory network derived from ENCODE data , 2012, Nature.

[57]  Michael B Atkins,et al.  Resistance to targeted therapy in renal-cell carcinoma. , 2009, The Lancet. Oncology.

[58]  L. Tsimring,et al.  A synchronized quorum of genetic clocks , 2009, Nature.

[59]  Russell M. Gordley,et al.  Engineering Customized Cell Sensing and Response Behaviors Using Synthetic Notch Receptors , 2016, Cell.

[60]  Liang Dong,et al.  An Efficient Light-Inducible P53 Expression System for Inhibiting Proliferation of Bladder Cancer Cell , 2016, International journal of biological sciences.

[61]  S. Monga,et al.  Novel Genetic Activation Screening in Liver Repopulation and Cancer: Now CRISPR Than Ever! , 2018, Hepatology.

[62]  Weiren Huang,et al.  Synthesizing a Genetic Sensor Based on CRISPR-Cas9 for Specifically Killing p53-Deficient Cancer Cells. , 2018, ACS synthetic biology.

[63]  David A. Scott,et al.  In vivo genome editing using Staphylococcus aureus Cas9 , 2015, Nature.

[64]  J. Concordet,et al.  CtIP fusion to Cas9 enhances transgene integration by homology-dependent repair , 2018, Nature Communications.

[65]  Jennifer A. Doudna,et al.  Conformational control of DNA target cleavage by CRISPR–Cas9 , 2015, Nature.

[66]  Georg Seelig,et al.  MicroRNA-based single-gene circuits buffer protein synthesis rates against perturbations. , 2014, ACS synthetic biology.

[67]  Ron Weiss,et al.  Highly-efficient Cas9-mediated transcriptional programming , 2014, Nature Methods.

[68]  Jennifer A. Doudna,et al.  New CRISPR-Cas systems from uncultivated microbes , 2016, Nature.

[69]  T. Lu,et al.  Genomically encoded analog memory with precise in vivo DNA writing in living cell populations , 2014, Science.

[70]  Luke A. Gilbert,et al.  CRISPR-Mediated Modular RNA-Guided Regulation of Transcription in Eukaryotes , 2013, Cell.

[71]  Christopher M. Vockley,et al.  Epigenome editing by a CRISPR/Cas9-based acetyltransferase activates genes from promoters and enhancers , 2015, Nature Biotechnology.

[72]  Feng Zhang,et al.  Crystal Structure of Cas9 in Complex with Guide RNA and Target DNA , 2014, Cell.

[73]  Eugene V Koonin,et al.  Discovery and Functional Characterization of Diverse Class 2 CRISPR-Cas Systems. , 2015, Molecular cell.