CRISPR-Cas9 for cancer therapy: Opportunities and challenges

Chen, Minjiang; Mao, Aiwu; Xu, Min; Weng, Qiaoyou; Mao, Jianghong; Ji, Jiansong

doi:10.1016/j.canlet.2019.01.017

Cited by 163 publications

(91 citation statements)

References 101 publications

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“…Unlike RNAi, which is mostly a post-transcriptional gene silencing mechanism, TALENs and CRISPRs have revolutionized genome engineering and have opened up new avenues of targeted therapy [175,[239][240][241]. Oncogenes and tumor suppressors can be manipulated using these techniques [241,242]. Again, their delivery has been a big challenge.…”

Section: Protein-based Effectorsmentioning

confidence: 99%

Oncolytic Adenoviruses: Strategies for Improved Targeting and Specificity

Hajeri

Sharma

Yamamoto

2020

Cancers

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Cancer is a major health problem. Most of the treatments exhibit systemic toxicity, as they are not targeted or specific to cancerous cells and tumors. Adenoviruses are very promising gene delivery vectors and have immense potential to deliver targeted therapy. Here, we review a wide range of strategies that have been tried, tested, and demonstrated to enhance the specificity of oncolytic viruses towards specific cancer cells. A combination of these strategies and other conventional therapies may be more effective than any of those strategies alone.

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Section: Protein-based Effectorsmentioning

confidence: 99%

Oncolytic Adenoviruses: Strategies for Improved Targeting and Specificity

Hajeri

Sharma

Yamamoto

2020

Cancers

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“…AttnToCrispr_CNN also takes advantage of the aforementioned deep learning techniques and demonstrates competitive performance on sgRNA efficiency prediction. More importantly, cells fitness concern after treatment with CRISPR-Cas system is another issue to be tackled for gene therapy application in addition to off-target side effect [51, 52]. The negative selection experiment data is a valuable resource to study the CRISPR-Cas system effect on the cellular response, specifically on cell growth.…”

Section: Discussionmentioning

confidence: 99%

Prediction of off-target specificity and cell-specific fitness of CRISPR-Cas System using attention boosted deep learning and network-based gene feature

Xie

2019

PLoS Comput Biol

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CRISPR-Cas is a powerful genome editing technology and has a great potential for in vivo gene therapy. Successful translational application of CRISPR-Cas to biomedicine still faces many safety concerns, including off-target side effect, cell fitness problem after CRISPR-Cas treatment, and on-target genome editing side effect in undesired tissues. To solve these issues, it is needed to design sgRNA with high cell-specific efficacy and specificity. Existing single-guide RNA (sgRNA) design tools mainly depend on a sgRNA sequence and the local information of the targeted genome, thus are not sufficient to account for the difference in the cellular response of the same gene in different cell types. To incorporate cell-specific information into the sgRNA design, we develop novel interpretable machine learning models, which integrate features learned from advanced transformer-based deep neural network with cell-specific gene property derived from biological network and gene expression profile, for the prediction of CRISPR-Cas9 and CRISPR-Cas12a efficacy and specificity. In benchmark studies, our models significantly outperform state-of-the-art algorithms. Furthermore, we find that the network-based gene property is critical for the prediction of cell-specific post-treatment cellular response. Our results suggest that the design of efficient and safe CRISPR-Cas needs to consider cell-specific information of genes. Our findings may bolster developing more accurate predictive models of CRISPR-Cas across a broad spectrum of biological conditions as well as provide new insight into developing efficient and safe CRISPR-based gene therapy.

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“… Cancer Cancer is the second leading cause of death worldwide after cardiovascular diseases, and it is also a medical problem that needs to be solved urgently. A variety of genetic or epigenetic mutations have been accumulated in the cancer genome, which can activate proto-oncogenes, inactivate tumor suppressors and produce drug resistance [209] , [210] . So far, CRISPR-Cas systems have been used to correct the oncogenic genome/epigenome mutations in tumor cells and animal models, resulting in inhibition of tumor cell growth and promotion of cell apoptosis, thereby inhibiting tumor growth [211] , [212] , [213] .…”

Section: Applications Of Crispr-cas Systems In Human Disease Researchmentioning

confidence: 99%

CRISPR-Cas systems: Overview, innovations and applications in human disease research and gene therapy

2020

Computational and Structural Biotechnology Journal

154

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Genome editing is the modification of genomic DNA at a specific target site in a wide variety of cell types and organisms, including insertion, deletion and replacement of DNA, resulting in inactivation of target genes, acquisition of novel genetic traits and correction of pathogenic gene mutations. Due to the advantages of simple design, low cost, high efficiency, good repeatability and short-cycle, CRISPR-Cas systems have become the most widely used genome editing technology in molecular biology laboratories all around the world. In this review, an overview of the CRISPR-Cas systems will be introduced, including the innovations, the applications in human disease research and gene therapy, as well as the challenges and opportunities that will be faced in the practical application of CRISPR-Cas systems.

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CRISPR-Cas9 for cancer therapy: Opportunities and challenges

Cited by 163 publications

References 101 publications

Oncolytic Adenoviruses: Strategies for Improved Targeting and Specificity

Oncolytic Adenoviruses: Strategies for Improved Targeting and Specificity

Prediction of off-target specificity and cell-specific fitness of CRISPR-Cas System using attention boosted deep learning and network-based gene feature

CRISPR-Cas systems: Overview, innovations and applications in human disease research and gene therapy

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