Directing cellular information flow via CRISPR signal conductors

Liu, Yuchen; Zhan, Yonghao; Chen, Zhicong; He, Anbang; Li, Jianfa; Wu, Hanwei; Liu, Li; Zhuang, Cheng‐Le; Lin, Junhao; Guo, Xiaoqiang; Zhang, Qiaoxia; Huang, Weiren; Cai, Zhiming

doi:10.1038/nmeth.3994

Cited by 161 publications

(137 citation statements)

References 41 publications

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“…By using aptazymes to remove blocking sequences that abrogate essential guide RNA structures, we have developed a set of small molecule-responsive agRNAs that enable exogenous control over genome engineering in mammalian cells using strategies that are complementary to other conditional Cas9 variants. In addition, small molecule-dependent guide RNAs have been reported in CRISPR ‘signal conductors’ to control gene expression for constructing logic gates and genetic circuits31. Our work serves as the first example to our knowledge of small molecule-controlled genome editing in mammalian cells achieved through guide RNA engineering.…”

Section: Discussionmentioning

confidence: 86%

Aptazyme-embedded guide RNAs enable ligand-responsive genome editing and transcriptional activation

2017

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Programmable sequence-specific genome editing agents such as CRISPR-Cas9 have greatly advanced our ability to manipulate the human genome. Although canonical forms of genome-editing agents and programmable transcriptional regulators are constitutively active, precise temporal and spatial control over genome editing and transcriptional regulation activities would enable the more selective and potentially safer use of these powerful technologies. Here, by incorporating ligand-responsive self-cleaving catalytic RNAs (aptazymes) into guide RNAs, we developed a set of aptazyme-embedded guide RNAs that enable small molecule-controlled nuclease-mediated genome editing and small molecule-controlled base editing, as well as small molecule-dependent transcriptional activation in mammalian cells.

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Section: Discussionmentioning

confidence: 86%

Aptazyme-embedded guide RNAs enable ligand-responsive genome editing and transcriptional activation

2017

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“…The advantage of using sgRNA-based inducible systems for synthetic biology applications has been recently showcased in a study demonstrating the ability to rewire cellular pathways by CRISPR-TR with modified sgRNAs containing ligand-responsive riboswitches29. These sgRNA ‘signal conductors' employ a strand-displacement mechanism to transition between OFF and ON states and can be coupled to a variety of inducers and dCas9 effectors.…”

Section: Discussionmentioning

confidence: 99%

Rational design of inducible CRISPR guide RNAs for de novo assembly of transcriptional programs

2017

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CRISPR-based transcription regulators (CRISPR-TRs) have transformed the current synthetic biology landscape by allowing specific activation or repression of any target gene. Here we report a modular and versatile framework enabling rapid implementation of inducible CRISPR-TRs in mammalian cells. This strategy relies on the design of a spacer-blocking hairpin (SBH) structure at the 5′ end of the single guide RNA (sgRNA), which abrogates the function of CRISPR-transcriptional activators. By replacing the SBH loop with ligand-controlled RNA-cleaving units, we demonstrate conditional activation of quiescent sgRNAs programmed to respond to genetically encoded or externally delivered triggers. We use this system to couple multiple synthetic and endogenous target genes with specific inducers, and assemble gene regulatory modules demonstrating parallel and orthogonal transcriptional programs. We anticipate that this ‘plug and play' approach will be a valuable addition to the synthetic biology toolkit, facilitating the understanding of natural gene circuits and the design of cell-based therapeutic strategies.

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“…[17][18][19] HOTAIR, MALAT-1, ATB, SPRY4-IT1 and CCAT2 are well-known oncogenic lncRNAs, which can induce tumourigenesis. 16,[20][21][22][23] LncRNAs take part in various aspects of cell biology and not doubt that contribute to tumour development potentially through stimulating or inhibiting cell proliferation, apoptosis, differentiation, invasion and metastasis. 24 Dysregulation of lncRNAs leads to tumour formation, contributing to cancer development, progression and metastasis.…”

Section: 10mentioning

confidence: 99%

Long non‐coding PANDAR as a novel biomarker in human cancer: A systematic review

Zou

Zhong

et al. 2017

Cell Proliferation

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Objectives: Long non-coding RNAs (lncRNAs) are characterized as a group of RNAs that more than 200 nucleotides in length and have no protein-coding function. More and more evidences provided that lncRNAs serve as key molecules in the development of cancer. Deregulation of lncRNAs functions as either oncogenes or tumour suppressor genes in various diseases. Recently, increasing studies about PANDAR in cancer progression were reported. In our review, we will focus on the current research on the character of PANDAR include the clinical management, tumour progression and molecular mechanisms in human cancers. Materials and methods:We summarize and analyze current studies concerning the biological functions and mechanisms of lncRNA PANDA in tumour development. The related studies were obtained through a systematic search of Pubmed.Results: PANDAR was a well-characterized oncogenic lncRNA and widely overexpressed in many tumours. PANDAR is upregulated in many types of cancer, including colorectal cancer, lung cancer, renal cell carcinoma, cholangiocarcinoma, osteosarcoma, thyroid cancer and other cancers. Upregulation of PANDAR was significantly associated with advanced tumour weights, TNM stage and overall survival. Furthermore, repressed of PANDAR would restrain proliferation, migration and invasion. Conclusion:PANDAR may act as a powerful tumour biomarker for cancer diagnosis and treatment.

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Directing cellular information flow via CRISPR signal conductors

Cited by 161 publications

References 41 publications

Aptazyme-embedded guide RNAs enable ligand-responsive genome editing and transcriptional activation

Aptazyme-embedded guide RNAs enable ligand-responsive genome editing and transcriptional activation

Rational design of inducible CRISPR guide RNAs for de novo assembly of transcriptional programs

Long non‐coding PANDAR as a novel biomarker in human cancer: A systematic review

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