Tumor cell-targeted delivery of CRISPR/Cas9 by aptamer-functionalized lipopolymer for therapeutic genome editing of VEGFA in osteosarcoma

Liang, Chao; Li, Fangfei; Wang, Luyao; Zhang, Zongkang; Wang, Chao; He, Bing; Li, Jie; Chen, Zhihao; Shaikh, Atik Badshah; Liu, Jin; Wu, Xiaohao; Peng, Songlin; Dang, Lei; Guo, Baosheng; He, Xiaojuan; Au, Doris W.T.; Lü, Cheng; Zhu, Hai; Zhang, Bao-Ting; Lü, Aiping; Zhang, Ge

doi:10.1016/j.biomaterials.2017.09.015

Cited by 164 publications

(100 citation statements)

References 74 publications

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“…For instance, the delivery of plasmid DNA encoding a Cas9-sgRNA complex that targets VEGF using a PEG-PEI-cholesterol lipid polymer could achieve a gene knockout of approximately 50% in osteosarcoma cells in vitro and in vivo. 327 A lipid delivery system containing PEG-poly lacticcoglycolic acid nanoparticles was used to deliver CRISPR DNA constructed by a CD68 promoter and achieve in vitro and in vivo Fig. 4 Viral and nonviral delivery systems for genome editing technology.…”

Section: Increasing the Specificity Of Gene Correctionmentioning

confidence: 99%

Applications of genome editing technology in the targeted therapy of human diseases: mechanisms, advances and prospects

Li¹,

Yang²,

Hong³

et al. 2020

Sig Transduct Target Ther

1,376

869

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Based on engineered or bacterial nucleases, the development of genome editing technologies has opened up the possibility of directly targeting and modifying genomic sequences in almost all eukaryotic cells. Genome editing has extended our ability to elucidate the contribution of genetics to disease by promoting the creation of more accurate cellular and animal models of pathological processes and has begun to show extraordinary potential in a variety of fields, ranging from basic research to applied biotechnology and biomedical research. Recent progress in developing programmable nucleases, such as zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeat (CRISPR)-Cas-associated nucleases, has greatly expedited the progress of gene editing from concept to clinical practice. Here, we review recent advances of the three major genome editing technologies (ZFNs, TALENs, and CRISPR/Cas9) and discuss the applications of their derivative reagents as gene editing tools in various human diseases and potential future therapies, focusing on eukaryotic cells and animal models. Finally, we provide an overview of the clinical trials applying genome editing platforms for disease treatment and some of the challenges in the implementation of this technology.

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Section: Increasing the Specificity Of Gene Correctionmentioning

confidence: 99%

Applications of genome editing technology in the targeted therapy of human diseases: mechanisms, advances and prospects

Li¹,

Yang²,

Hong³

et al. 2020

Sig Transduct Target Ther

1,376

869

View full text Add to dashboard Cite

show abstract

“…In this research, CRISPR/Cas9 plasmids encoding Cas9 proteins and sgRNA targeting vascular endothelial growth factor A (VEGFA) were loaded into PEG‐polyethylenimine‐cholesterol lipopolymers, which were modified with the osteosarcoma (OS) cell‐specific aptamer (LC09) to increase OS tumor‐selective delivery. VEGFA is highly expressed in OS cells, and the inhibition of VEGFA expression can improve symptoms of poor prognosis, such as orthotopic OS growth and bone lesions …”

Section: Non‐viral Vectors Of Crispr‐cas9mentioning

confidence: 99%

“…The mice were treated by intravenous injection of CLANs to disrupt the expression of netrin-1 genes in monocytes and macrophages specifically, and the results obtained suggested that this could reduce macrophage retention and ameliorate the profiles of glucose tolerance and insulin sensitivity to control T2D ( Figure 5D). 122 Recently, Liang et al 132 126 Recently, a facile method to construct a multifunctional vector that can deliver CRISPR/Cas9 plasmids into cancer cells was also developed. The gene-editing tools were delivered into cancer cells for the disruption of CTNNB1 genes.…”

Section: Polymer-mediated Cas9 Plasmid Deliverymentioning

confidence: 99%

Delivery of CRISPR/Cas9 for therapeutic genome editing

Wan

Xin

et al. 2019

The Journal of Gene Medicine

101

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The clustered, regularly‐interspaced, short palindromic repeat (CRISPR)‐associated nuclease 9 (CRISPR/Cas9) is emerging as a promising genome‐editing tool for treating diseases in a precise way, and has been applied to a wide range of research in the areas of biology, genetics, and medicine. Delivery of therapeutic genome‐editing agents provides a promising platform for the treatment of genetic disorders. Although viral vectors are widely used to deliver CRISPR/Cas9 elements with high efficiency, they suffer from several drawbacks, such as mutagenesis, immunogenicity, and off‐target effects. Recently, non‐viral vectors have emerged as another class of delivery carriers in terms of their safety, simplicity, and flexibility. In this review, we discuss the modes of CRISPR/Cas9 delivery, the barriers to the delivery process and the application of CRISPR/Cas9 system for the treatment of genetic disorders. We also highlight several representative types of non‐viral vectors, including polymers, liposomes, cell‐penetrating peptides, and other synthetic vectors, for the therapeutic delivery of CRISPR/Cas9 system. The applications of CRISPR/Cas9 in treating genetic disorders mediated by the non‐viral vectors are also discussed.

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“…Receptor-mediated transfection offers an attractive means to achieve preferential accumulation and increased efficacy of a therapeutic unit (8-11). Recently, small molecule ligands (12) and aptamers (13) have been coupled to the Cas9 protein or a Cas9 containing nanoparticle, respectively, for receptor-mediated uptake into cells. The potential to specifically deliver Cas9 RNP to cells overexpressing a particular receptor type offers many opportunities for targeting the effects of gene editing specifically towards disease-causing cells.…”

Section: Introductionmentioning

confidence: 99%

Receptor Mediated Delivery of Cas9-Nanobody Induces Cisplatin Synthetic Dose Sensitivity

Roche

Olesen

Hussain

et al. 2018

Preprint

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26The CRISPR/Cas9 system has shown great potential for precisely editing genomic DNA 27 sequences by introducing site-specific DNA cuts that are subsequently repaired by the cell. 28However, delivery of the CRISPR ribonucleoprotein remains an understudied area and hinders 29 realizing the full potential of the system. We prepared Cas9 ribonucleoprotein complexes 30 chemically conjugated to the 7D12 nanobody and demonstrate receptor-mediated transfection of 31Cas9 into A549 non-small-cell lung cancer cells via binding to the epithelial growth factor receptor 32 for subsequent cell internalization. We further show that transfection with a Cas9 33 ribonucleoprotein targeting the BRCA2 gene results in an enhanced sensitivity to the 34 chemotherapeutic drug Cisplatin, and thereby induces a synthetic dose lethality in A549 cells. 35 36

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Tumor cell-targeted delivery of CRISPR/Cas9 by aptamer-functionalized lipopolymer for therapeutic genome editing of VEGFA in osteosarcoma

Cited by 164 publications

References 74 publications

Applications of genome editing technology in the targeted therapy of human diseases: mechanisms, advances and prospects

Applications of genome editing technology in the targeted therapy of human diseases: mechanisms, advances and prospects

Delivery of CRISPR/Cas9 for therapeutic genome editing

Receptor Mediated Delivery of Cas9-Nanobody Induces Cisplatin Synthetic Dose Sensitivity

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