Current applications and future perspective of CRISPR/Cas9 gene editing in cancer

Wang, Siwei; Gao, Chao; Zheng, Yi-Min; Li, Yang; Lu, Jia‐Cheng; Huang, Xiaoyong; Cai, Jia‐Bin; Zhang, Peng-Fei; Cui, Yuehong; Ke, Ai–Wu

doi:10.1186/s12943-022-01518-8

Cited by 151 publications

(110 citation statements)

References 217 publications

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“…CRISPR/Cas9 is a common gene-editing tool that uses RNA-guided nucleases to cleave foreign genetic elements. 300 – 307 CRISPR/Cas9 may serve as a potential method to target unique eccDNA breakpoint sequences, although it still lacks experimental evidence. 300 , 301 , 308 , 309 The effects of CRISPR/Cas9 on the elimination of eccDNA need to be further explored.…”

Section: Limitations Of Eccdnamentioning

confidence: 99%

Extrachromosomal circular DNA: biogenesis, structure, functions and diseases

Yang

Jia

et al. 2022

Sig Transduct Target Ther

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Extrachromosomal circular DNA (eccDNA), ranging in size from tens to millions of base pairs, is independent of conventional chromosomes. Recently, eccDNAs have been considered an unanticipated major source of somatic rearrangements, contributing to genomic remodeling through chimeric circularization and reintegration of circular DNA into the linear genome. In addition, the origin of eccDNA is considered to be associated with essential chromatin-related events, including the formation of super-enhancers and DNA repair machineries. Moreover, our understanding of the properties and functions of eccDNA has continuously and greatly expanded. Emerging investigations demonstrate that eccDNAs serve as multifunctional molecules in various organisms during diversified biological processes, such as epigenetic remodeling, telomere trimming, and the regulation of canonical signaling pathways. Importantly, its special distribution potentiates eccDNA as a measurable biomarker in many diseases, especially cancers. The loss of eccDNA homeostasis facilitates tumor initiation, malignant progression, and heterogeneous evolution in many cancers. An in-depth understanding of eccDNA provides novel insights for precision cancer treatment. In this review, we summarized the discovery history of eccDNA, discussed the biogenesis, characteristics, and functions of eccDNA. Moreover, we emphasized the role of eccDNA during tumor pathogenesis and malignant evolution. Therapeutically, we summarized potential clinical applications that target aberrant eccDNA in multiple diseases.

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Section: Limitations Of Eccdnamentioning

confidence: 99%

Extrachromosomal circular DNA: biogenesis, structure, functions and diseases

Yang

Jia

et al. 2022

Sig Transduct Target Ther

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“…The entire genome sequencing of mice cells showed that there were a high number of mutations after editing by CRISPR/Cas9 [121]. The off-target effect of CRISPR/Cas9 has been demonstrated in functional studies of plant genome [109,122] and clinical applications [123][124][125], indicating the CRISPR/Cas9 system's off-target effect to be a widespread phenomenon. There are two main kinds of mismatches between sgRNA and the target DNA.…”

Section: Off-target Effectmentioning

confidence: 99%

Advances in CRISPR/Cas9

Zhu

2022

BioMed Research International

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CRISPR/Cas9 technology has become the most examined gene editing technology in recent years due to its simple design, yet low cost, high efficiency, and simple operation, which can also achieve simultaneous editing of multiple loci. It can also be carried out without using plasmids, saving lots of troubles caused by plasmids. CRISPR/Cas9 has shown great potential in the study of genes or genomic functions in microorganisms, plants, animals, and human beings. In this review, we will examine the history, structure, and basic mechanisms of the CRISPR/Cas9 system, describe its great value in precision medicine and sgRNA library screening, and dig its great potential in a new field: DNA information storage.

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“…Although CRISPR-Cas9 delivery by using MSNs is in an initial stage and challenges still remain, the versatility of this type of nanomaterial allows multiple combinations for gene editing by carrying plasmids, sgRNA, and Cas9 mRNA, or directly the Cas9 protein. Moreover, targeting ligands can be easily incorporated into MSNs to achieve targeted CRISPR-Cas9 delivery to thus reduce the off-target effects that derive from gene editing in non-targeted tissues [ 64 ]. Importantly as a dual platform, multiple combinations for gene editing and drug therapy can be envisioned by using MSNs by preparing advanced nanodevices to solve possible biomedical needs in complex diseases or restoring sensitivity in drug-resistant diseases like cancer or infections [ 64 , 65 , 66 ].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, targeting ligands can be easily incorporated into MSNs to achieve targeted CRISPR-Cas9 delivery to thus reduce the off-target effects that derive from gene editing in non-targeted tissues [ 64 ]. Importantly as a dual platform, multiple combinations for gene editing and drug therapy can be envisioned by using MSNs by preparing advanced nanodevices to solve possible biomedical needs in complex diseases or restoring sensitivity in drug-resistant diseases like cancer or infections [ 64 , 65 , 66 ].…”

Section: Discussionmentioning

confidence: 99%

Nanodevices for the Efficient Codelivery of CRISPR-Cas9 Editing Machinery and an Entrapped Cargo: A Proposal for Dual Anti-Inflammatory Therapy

et al. 2022

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In this article, we report one of the few examples of nanoparticles capable of simultaneously delivering CRISPR-Cas9 gene-editing machinery and releasing drugs for one-shot treatments. Considering the complexity of inflammation in diseases, the synergistic effect of nanoparticles for gene-editing/drug therapy is evaluated in an in vitro inflammatory model as proof of concept. Mesoporous silica nanoparticles (MSNs), able to deliver the CRISPR/Cas9 machinery to edit gasdermin D (GSDMD), a key protein involved in inflammatory cell death, and the anti-inflammatory drug VX-765 (GSDMD45CRISPR-VX-MSNs), were prepared. Nanoparticles allow high cargo loading and CRISPR-Cas9 plasmid protection and, thus, achieve the controlled codelivery of CRISPR-Cas9 and the drug in cells. Nanoparticles exhibit GSDMD gene editing by downregulating inflammatory cell death and achieving a combined effect on decreasing the inflammatory response by the codelivery of VX-765. Taken together, our results show the potential of MSNs as a versatile platform by allowing multiple combinations for gene editing and drug therapy to prepare advanced nanodevices to meet possible biomedical needs.

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Current applications and future perspective of CRISPR/Cas9 gene editing in cancer

Cited by 151 publications

References 217 publications

Extrachromosomal circular DNA: biogenesis, structure, functions and diseases

Extrachromosomal circular DNA: biogenesis, structure, functions and diseases

Advances in CRISPR/Cas9

Nanodevices for the Efficient Codelivery of CRISPR-Cas9 Editing Machinery and an Entrapped Cargo: A Proposal for Dual Anti-Inflammatory Therapy

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