Genome Editing in a Wide Area of the Brain Using Dendrimer-Based Ternary Polyplexes of Cas9 Ribonucleoprotein

Taharabaru, Toru; Yokoyama, Ryoma; Higashi, Taishi; Mohammed, Ahmed Fouad Abdelwahab; Inoue, Masamichi; Maeda, Yuki; Niidome, Takuro; Onodera, Risako; Motoyama, Keiichi

doi:10.1021/acsami.9b21667

Cited by 26 publications

(15 citation statements)

References 65 publications

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“…Dendrimers are a class of synthetic polymer with a spherical and hyperbranched structure, whose surface is functionalized with a high density of phenylboronic acid moieties to ensure that RNPs are efficiently bound to the dendrimer scaffold and transmit RNP to specific cells (Dixit et al, 2014). As a novel therapeutic tool for genetic disorders, dendrimers allow the efficient delivery of RNP targeting multiple genetic loci in different cell lines, proving to be a useful material for the delivery of genome-editing tools with broad biomedical applications (Taharabaru et al, 2020). Several issues exist with RNP delivery using polymers, however, such as low efficiency, high cytotoxicity, and narrow application range, which need to be overcome in the future.…”

Section: Polymersmentioning

confidence: 99%

Strategies for High-Efficiency Mutation Using the CRISPR/Cas System

Feng

Wang

et al. 2022

Front. Cell Dev. Biol.

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Clustered regularly interspaced short palindromic repeats (CRISPR)-associated systems have revolutionized traditional gene-editing tools and are a significant tool for ameliorating gene defects. Characterized by high target specificity, extraordinary efficiency, and cost-effectiveness, CRISPR/Cas systems have displayed tremendous potential for genetic manipulation in almost any organism and cell type. Despite their numerous advantages, however, CRISPR/Cas systems have some inherent limitations, such as off-target effects, unsatisfactory efficiency of delivery, and unwanted adverse effects, thereby resulting in a desire to explore approaches to address these issues. Strategies for improving the efficiency of CRISPR/Cas-induced mutations, such as reducing off-target effects, improving the design and modification of sgRNA, optimizing the editing time and the temperature, choice of delivery system, and enrichment of sgRNA, are comprehensively described in this review. Additionally, several newly emerging approaches, including the use of Cas variants, anti-CRISPR proteins, and mutant enrichment, are discussed in detail. Furthermore, the authors provide a deep analysis of the current challenges in the utilization of CRISPR/Cas systems and the future applications of CRISPR/Cas systems in various scenarios. This review not only serves as a reference for improving the maturity of CRISPR/Cas systems but also supplies practical guidance for expanding the applicability of this technology.

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Section: Polymersmentioning

confidence: 99%

Strategies for High-Efficiency Mutation Using the CRISPR/Cas System

Feng

Wang

et al. 2022

Front. Cell Dev. Biol.

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“…However, Cas9 RNP generally also has low cell membrane permeability; thus, an efficient intracellular delivery system for Cas9 RNP is urgently required [ 97 ]. In recent years, several researchers have developed Cas9 RNP delivery systems [ 98 , 99 ]. Therefore, genome editing that occurs within a narrow range of the injection area requires multiple invasive injections in different brain areas.…”

Section: Gug-β-cde For Genome Editingmentioning

confidence: 99%

“…In addition, GUG-β-CDE (G3, DSC3) enhanced the genome editing activity of Cas9 RNP in the whole mouse brain after a single intraventricular administration. Thus, GUG-β-CDE (G3, DSC3) is a useful Cas9 RNP carrier that can induce genome editing in the neuron and brain [ 99 ]. Table 4 shows various CDEs introduced in the review.…”

Section: Gug-β-cde For Genome Editingmentioning

confidence: 99%

Twenty Years of Research on Cyclodextrin Conjugates with PAMAM Dendrimers

Arima

2021

Pharmaceutics

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Recently, the number of gene and oligonucleotide drugs are increasing. Of various drug delivery systems (DDSs) for gene and oligonucleotide drugs, few examples of the clinical application of polymer as drug carriers are known, despite development of the novel polymers has been progressing. Cyclodextrin (CD) conjugates with starburst polyamidoamine (PAMAM) dendrimer (CDEs), as a new type of polymer-based carriers, were first published in 2001. After that, galactose-, lactose-, mannose-, fucose-, folate-, and polyethyleneglycol (PEG)-appended CDEs have been prepared for passive and active targeting for gene, oligonucleotide, and low-molecular-weight drugs. PEG-appended CDE formed polypsuedorotaxanes with α-CD and γ-CD, which are useful for a sustained release system of gene and oligonucleotide drugs. Interestingly, CDEs were found to have anti-inflammatory effects and anti-amyloid effects themselves, which have potential as active pharmaceutical ingredients. Most recently, CDE is reported to be a useful Cas9-RNA ribonucleoproteins (Cas9 RNP) carrier that induces genome editing in the neuron and brain. In this review, the history and progression of CDEs are overviewed.

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“…Glucuronylglucosyl-mediated endosomal escape has been studied for achieving efficient genome editing in the brain [132]. In this study, a dendrimer containing glucuronylglucosyl-β-CD conjugate was used as a Cas9/sgRNA ribonucleoprotein delivery system.…”

Section: Chemical/peptide-enhanced Deliverymentioning

confidence: 99%

Nanovesicle-Mediated Delivery Systems for CRISPR/Cas Genome Editing

Kim

et al. 2020

Pharmaceutics

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Genome-editing technology has emerged as a potential tool for treating incurable diseases for which few therapeutic modalities are available. In particular, discovery of the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system together with the design of single-guide RNAs (sgRNAs) has sparked medical applications of genome editing. Despite the great promise of the CRISPR/Cas system, its clinical application is limited, in large part, by the lack of adequate delivery technology. To overcome this limitation, researchers have investigated various systems, including viral and nonviral vectors, for delivery of CRISPR/Cas and sgRNA into cells. Among nonviral delivery systems that have been studied are nanovesicles based on lipids, polymers, peptides, and extracellular vesicles. These nanovesicles have been designed to increase the delivery of CRISPR/Cas and sgRNA through endosome escape or using various stimuli such as light, pH, and environmental features. This review covers the latest research trends in nonviral, nanovesicle-based delivery systems that are being applied to genome-editing technology and suggests directions for future progress.

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Genome Editing in a Wide Area of the Brain Using Dendrimer-Based Ternary Polyplexes of Cas9 Ribonucleoprotein

Cited by 26 publications

References 65 publications

Strategies for High-Efficiency Mutation Using the CRISPR/Cas System

Strategies for High-Efficiency Mutation Using the CRISPR/Cas System

Twenty Years of Research on Cyclodextrin Conjugates with PAMAM Dendrimers

Nanovesicle-Mediated Delivery Systems for CRISPR/Cas Genome Editing

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