Nanoparticle-Based Delivery of CRISPR/Cas9 Genome-Editing Therapeutics

Givens, Brittany E.; Naguib, Youssef W.; Geary, Sean M.; Devor, Eric J.; Salem, Aliasger K.

doi:10.1208/s12248-018-0267-9

Cited by 80 publications

(64 citation statements)

References 178 publications

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Section: Mechanism Of Cpp-uptake and Releasementioning

confidence: 99%

“…After endocytosis, internalized material is found in endosomes (pH 6.5–6.8), which develop to be late endosomes (pH 5.2–6.0), before moving into lysosomes (pH 4.5–5.2) where it is subjected to degradation by enzymes and the acidic environment ( Figure 4 B) [ 155 ]. Endosomal escape is considered to be the bottleneck in the development of most non-viral vectors, including CPPs, with very low endosomal escape efficiencies [ 155 , 156 ]. This has been reported, in many studies employing CPPs to deliver plasmids, proteins or siRNA, as punctate distribution of the internalized CPPs, suggesting that they are remaining within endosomal vesicles [ 157 , 158 , 159 ].…”

Section: Mechanism Of Cpp-uptake and Releasementioning

confidence: 99%

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Tissue-Specific Delivery of CRISPR Therapeutics: Strategies and Mechanisms of Non-Viral Vectors

Shalaby

Aouida

El‐Agnaf

2020

IJMS

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The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) genome editing system has been the focus of intense research in the last decade due to its superior ability to desirably target and edit DNA sequences. The applicability of the CRISPR-Cas system to in vivo genome editing has acquired substantial credit for a future in vivo gene-based therapeutic. Challenges such as targeting the wrong tissue, undesirable genetic mutations, or immunogenic responses, need to be tackled before CRISPR-Cas systems can be translated for clinical use. Hence, there is an evident gap in the field for a strategy to enhance the specificity of delivery of CRISPR-Cas gene editing systems for in vivo applications. Current approaches using viral vectors do not address these main challenges and, therefore, strategies to develop non-viral delivery systems are being explored. Peptide-based systems represent an attractive approach to developing gene-based therapeutics due to their specificity of targeting, scale-up potential, lack of an immunogenic response and resistance to proteolysis. In this review, we discuss the most recent efforts towards novel non-viral delivery systems, focusing on strategies and mechanisms of peptide-based delivery systems, that can specifically deliver CRISPR components to different cell types for therapeutic and research purposes.

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Section: Mechanism Of Cpp-uptake and Releasementioning

confidence: 99%

Section: Mechanism Of Cpp-uptake and Releasementioning

confidence: 99%

Tissue-Specific Delivery of CRISPR Therapeutics: Strategies and Mechanisms of Non-Viral Vectors

Shalaby

Aouida

El‐Agnaf

2020

IJMS

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“…Gene editing methods that are highly efficient like CRISPR or ZFNs are delivered via viral vectors and by interrupting CCR5, the CCR5 co-receptors become unavailable to HIV virus. CRISPR-Cas9 mediated systems that are delivered via non-viral vectors have also been developed including liposome like lipid based reagents (Cardarelli, et al 2016), polymer polyethyleneimine (PEI) and nanoparticle based (Givens, et al 2018) systems. However, since non-viral methods have lower efficiency, studies on improving the efficiency of the delivery have been done such as in a study where mouse models were being studied.…”

Section: Where Crispr-cas9 Falls Shortmentioning

confidence: 99%

“…For generating less cytotoxic side effects many novel nanoparticle investigations are being done for carrying CRISPR-Cas9 mediated systems into cells. When formulated differently, nanoparticles might have predilections for different tissues and organs such as liposome based ones being more preferable for lungs while different particles will be more suited for liver (Givens, et al 2018).…”

Section: Can Akpinaroglu / Gene Editingmentioning

confidence: 99%

AIDS tedavisi için gen düzenleme çalışmaları

Akpınaroğlu¹

2020

genediting

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Following after the fatal genetic diseases that were caused by single nucleotide polymorphisms (SNPs) and cancer, HIV/AIDS had always been one of the primary targets of cell and gene therapies due to lack of any proper satisfactory treatment. Earlier gene therapy approaches were mostly trials about introducing anti-HIV genes to cells, using various viral vectors. These viral vectors performed integrations of the desired anti-HIV genes, sometimes correctly while sometimes between random wrong sequences. However, with the increased precision of new gene editing technologies, including ZFNs and the latest CRISPR-mediated gene editing systems (Clustered Regularly Interspaced Short Palindromic Repeats) more successful therapies have begun to be administrated. As an important example of therapy, the trial of Timothy Ray Brown which was followed by the "London patient", allowed the topic of gene editing techniques for treatment of HIV and AIDS to gain interest again. Can Akpinaroglu / Gene Editing Creative Commons Attribution 4.0 International License. www.genediting.net

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“…[10] Additionally, it has been reported that up to 70% of patients could have pre-existing immunity to AAV, which may limit it's efficacy as a therapy. [15] Depending on the type of material used, nanocarriers have the ability to carry different types of cargo and can be chemically modified for colloidal stability, biodegradability, biocompatibility, and tissue specificity. [12] This sustained expression of bacterially derived Cas9 has the potential to enhance off-target activity or to prompt an immune response against Cas9 and the muscle.…”

mentioning

confidence: 99%

Polyrotaxane Nanocarriers Can Deliver CRISPR/Cas9 Plasmid to Dystrophic Muscle Cells to Successfully Edit the DMD Gene

Emami

Young

et al. 2019

Advanced Therapeutics

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Gene editing with clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9 (CRISPR/Cas9) has shown promise in models of Duchenne muscular dystrophy (DMD); however, nonviral strategies to deliver CRISPR to muscle have not been widely explored or optimized. Most studies have relied on viral vectors, which are likely limited to single dosing due to their immunogenicity, thus reducing their therapeutic potential. Therefore, there is a need to develop nonviral approaches that allow for delivery and repeat dosing of CRISPR/Cas9 therapies to skeletal muscle. Here, biocompatible multi-arm polyrotaxane (PRX) nanocarriers, are iteratively optimized for packaging large plasmid DNA for delivery to muscle cells. The PRXs are optimized by addition of a disulfide-responsive linker that enhances plasmid release. Furthermore, conjugation of peptides leads to quicker uptake and improved transfection efficiency in humanized dystrophic muscle cells in vitro. Finally, in vitro delivery of PRXs complexed with a CRISPR/Cas9 platform demonstrates effective deletion of DMD exons 45-55, a therapeutic strategy with potential to restore the reading frame for half of DMD patients. This work represents the first PRX platform that is optimized and designed for delivery of large plasmid DNA, such as CRISPR/Cas9, to dystrophic muscle cells.

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Nanoparticle-Based Delivery of CRISPR/Cas9 Genome-Editing Therapeutics

Cited by 80 publications

References 178 publications

Tissue-Specific Delivery of CRISPR Therapeutics: Strategies and Mechanisms of Non-Viral Vectors

Tissue-Specific Delivery of CRISPR Therapeutics: Strategies and Mechanisms of Non-Viral Vectors

AIDS tedavisi için gen düzenleme çalışmaları

Polyrotaxane Nanocarriers Can Deliver CRISPR/Cas9 Plasmid to Dystrophic Muscle Cells to Successfully Edit the DMD Gene

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