Artificial Virus Delivers CRISPR-Cas9 System for Genome Editing of Cells in Mice

Li, Ling; Song, Linjiang; Liu, Xiaowei; Yang, Xi; Li, Xia; He, Tao; Wang, Ning; Yang, Shuaijun; Chen, Yu; Yin, Tao; Yan, Wen; He, Zhiyao; Wei, Xiawei; Su, Weijun; Wu, Qinjie; Yao, Su; Gong, Changyang; Wei, Yuquan

doi:10.1021/acsnano.6b04261

Cited by 206 publications

(139 citation statements)

References 56 publications

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“…This system mediated efficient delivery of large-size CRISPR-Cas9 plasmid in vivo 38. In this study, we chose TRAIL as a therapeutic gene for colon cancer.…”

Section: Introductionmentioning

confidence: 99%

Multifunctional Nucleus-targeting Nanoparticles with Ultra-high Gene Transfection Efficiency for In Vivo Gene Therapy

Li¹,

Li²,

Wu³

et al. 2017

Theranostics

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Cancer stem cell-like cells (CSCL) are responsible for tumor recurrence associated with conventional therapy (e.g. surgery, radiation, and chemotherapy). Here, we developed a novel multifunctional nucleus-targeting nanoparticle-based gene delivery system which is capable of targeting and eradicating CSCL. These nanoparticles can facilitate efficient endosomal escape and spontaneously penetrate into nucleus without additional nuclear localization signal. They also induced extremely high gene transfection efficiency (>95%) even in culture medium containing 30% serum, which significantly surpassed that of some commercial transfection reagents, such as Lipofectamine 2000 and Lipofectamine 3000 etc. Especially, when loaded with the TRAIL gene, this system mediated remarkable depletion of CSCL. Upon systemic administration, the nanoparticles accumulated in tumor sites while sparing the non-cancer tissues and significantly inhibited the growth of tumors with no evident systemic toxicity. Taken together, our results suggest that these novel multifunctional, nucleus-targeting nanoparticles are a very promising in vivo gene delivery system capable of targeting CSCL and represent a new treatment candidate for improving the survival of cancer patients.

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“…This system mediated efficient delivery of large-size CRISPR-Cas9 plasmid in vivo 38. In this study, we chose TRAIL as a therapeutic gene for colon cancer.…”

Section: Introductionmentioning

confidence: 99%

Multifunctional Nucleus-targeting Nanoparticles with Ultra-high Gene Transfection Efficiency for In Vivo Gene Therapy

Li¹,

Li²,

Wu³

et al. 2017

Theranostics

Self Cite

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“…RRPHC contained the mixed components of hyaluronan (HA) and R8‐RGD tandem peptide, which endow the merits of intracellular penetrating ability and the targeting function of the nanocarrier. CRISPR/Cas9 plasmid was delivered by RRPHC to knock down the expression of the MutT homolog1 (MTH1), which resulted in more oxidized dNTP accumulation in the ovarian cancer peritoneal metastasis model to induce tumor apoptosis (Figure A) . In another study, Wang et al .…”

Section: Non‐viral Vectors Of Crispr‐cas9mentioning

confidence: 99%

“…(A) A multifunctional nucleus‐targeting “core‐shell” artificial virus (RRPHC) was constructed for the delivery of a CRISPR‐Cas9 system that can effectively target ovarian cancer. Reproduced with permission . (B) Cationic α ‐helical polypeptide poly( γ ‐4‐((2‐(piperidin‐1‐yl)ethyl)aminomethyl)benzyl‐ l ‐glutamate) (P‐HNPs) for the delivery of Cas9 expression plasmids and sgRNA targeting the polo‐like kinase 1 ( Plk1 ) genes.…”

Section: Non‐viral Vectors Of Crispr‐cas9mentioning

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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“…Most importantly, the perfluoroalkane chains are bio-inert and resistant to proteins, thus allowing the fluoroalkylated-containing amphiphilic polymer to achieve high transfection efficiency for gene delivery even in the presence of serum. 35,[59][60][61][62] This property is an essential characteristic for in vivo gene delivery.…”

Section: The Key Factors Of Micelles As Gene Carriersmentioning

confidence: 99%

Cationic micelle: A promising nanocarrier for gene delivery with high transfection efficiency

Wang

Ding

Zhang

et al. 2019

The Journal of Gene Medicine

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Micelles have demonstrated an excellent ability to deliver several different types of therapeutic agents, including chemotherapy drugs, proteins, small‐interfering RNA and DNA, into tumor cells. Cationic micelles, comprising self‐assemblies of amphiphilic cationic polymers, have exhibited tremendous promise with respect to the delivery of therapy genes and gene transfection. To date, research in the field has focused on achieving an enhanced stability of the micellar assembly, prolonged circulation times and controlled release of the gene. This review focuses on the micelles as a nanosized carrier system for gene delivery, the system‐related modifications for cytoplasm release, stability and biocompatibility, and clinic trials. In accordance with the development of synthetic chemistry and self‐assembly technology, the structures and functionalities of micelles can be precisely controlled, and hence the synthetic micelles not only efficiently condense DNA, but also facilitate DNA endocytosis, endosomal escape, DNA uptake and nuclear transport, resulting in a comparable gene transfection of virus.

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Artificial Virus Delivers CRISPR-Cas9 System for Genome Editing of Cells in Mice

Cited by 206 publications

References 56 publications

Multifunctional Nucleus-targeting Nanoparticles with Ultra-high Gene Transfection Efficiency for In Vivo Gene Therapy

Multifunctional Nucleus-targeting Nanoparticles with Ultra-high Gene Transfection Efficiency for In Vivo Gene Therapy

Delivery of CRISPR/Cas9 for therapeutic genome editing

Cationic micelle: A promising nanocarrier for gene delivery with high transfection efficiency

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