Abstract
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.
Highlights
Advances in synthetic biology and bioinfor‐ matics have been made in the design of reasonable and efficient ar‐ tificial gene signalling circuits with desired functionality.[1]
We conducted a systematic review of gene circuit development based on clustered regularly interspaced short palindromic repeat (CRISPR) technology and summarized the applications of gene circuits in tumour treatments
Scientists have developed a series of efficient and targeted transcrip‐ tion factor components based on CRISPR technology
Summary
Advances in synthetic biology and bioinfor‐ matics have been made in the design of reasonable and efficient ar‐ tificial gene signalling circuits with desired functionality.[1]. Compared with traditional gene editing tools, such as transcrip‐ tion activator‐like effector nucleases (TALENs) and zinc‐finger nucleases (ZFNs), CRISPR Cas[9] technology is efficient and convenient and has an ability to regulate multiple targets simultaneously within single cell.[47] The dCas[9] protein fused with transcriptional repressing or transcriptional activating domains were used to downregulate or upregulate specific single genes. Current studies have shown that gene circuits based on CRISPR/Cas technology can intelligently modify intracellular signal networks, regulate gene expression from the DNA level and inhibit the growth and development of tumour cells, the clinical applica‐ tions are still not currently available. CRISPR Cas[9] technology currently remains one of the most powerful genome editing tools, but its limitations are not to be ignored and should be addressed in the future
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