Material solutions for delivery of CRISPR/Cas-based genome editing tools: Current status and future outlook

Wan, Tao; Niu, Dong; Wu, Chuanbin; Xu, Fu‐Jian; Church, George M.; Yuan, Ping

doi:10.1016/j.mattod.2018.12.003

Cited by 98 publications

(75 citation statements)

References 202 publications

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“…Despite the excitement around the use of nucleic acid-based RNA interference and gene editing 44 , delivery remains the major challenge. Delivery systems for gene editing therapies include cationic lipids such as lipofectamine, liposomes, cationic polymers such as branched PEI, cationic gold based hybrid nanoparticles, and the use of cell penetrating peptides 45,46 . For example, a recent work utilizing a gold nanoparticle conjugated to cationic polymers for RNP delivery achieved 11.3% efficiency in editing blue fluorescent protein expressing HEK293 cells to express GFP via homology directed repair 47 .…”

Section: Discussionmentioning

confidence: 99%

An anionic, endosome-escaping polymer to potentiate intracellular delivery of cationic peptides, biomacromolecules, and nanoparticles

et al. 2019

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Peptides and biologics provide unique opportunities to modulate intracellular targets not druggable by conventional small molecules. Most peptides and biologics are fused with cationic uptake moieties or formulated into nanoparticles to facilitate delivery, but these systems typically lack potency due to low uptake and/or entrapment and degradation in endolysosomal compartments. Because most delivery reagents comprise cationic lipids or polymers, there is a lack of reagents specifically optimized to deliver cationic cargo. Herein, we demonstrate the utility of the cytocompatible polymer poly(propylacrylic acid) (PPAA) to potentiate intracellular delivery of cationic biomacromolecules and nano-formulations. This approach demonstrates superior efficacy over all marketed peptide delivery reagents and enhances delivery of nucleic acids and gene editing ribonucleoproteins (RNPs) formulated with both commercially-available and our own custom-synthesized cationic polymer delivery reagents. These results demonstrate the broad potential of PPAA to serve as a platform reagent for the intracellular delivery of cationic cargo.

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Section: Discussionmentioning

confidence: 99%

An anionic, endosome-escaping polymer to potentiate intracellular delivery of cationic peptides, biomacromolecules, and nanoparticles

et al. 2019

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“…Non‐viral vectors with a better safety profile usually do not possess sufficient transfection efficiency. [ 7–12 ] The reported non‐viral vectors cover diverse materials such as lipid‐like materials, [ 13,14 ] cell exosomes, [ 15 ] polymers and their hybrids, [ 16–22 ] nucleic acid based materials, [ 23 ] and metal containing materials. [ 24–26 ] Nevertheless, in spite of extensive studies on functionalization of non‐viral vectors, the studies on the vectors for delivery of genome editing plasmids are relatively rare.…”

Section: Methodsmentioning

confidence: 99%

Aptamer/Peptide‐Functionalized Genome‐Editing System for Effective Immune Restoration through Reversal of PD‐L1‐Mediated Cancer Immunosuppression

et al. 2020

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Effective reversal of tumor immunosuppression is of critical importance in cancer therapy. A multifunctional delivery vector that can effectively deliver CRISPR‐Cas9 plasmid for β‐catenin knockout to reverse tumor immunosuppression is constructed. The multi‐functionalized delivery vector is decorated with aptamer‐conjugated hyaluronic acid and peptide‐conjugated hyaluronic acid to combine the tumor cell/nuclear targeting function of AS1411 with the cell penetrating/nuclear translocation function of TAT‐NLS. Due to the significantly enhanced plasmid enrichment in malignant cell nuclei, the genome editing system can induce effective β‐catenin knockout and suppress Wnt/β‐catenin pathway, resulting in notably downregulated proteins involved in tumor progression and immunosuppression. Programmed death‐ligand 1 (PD‐L1) downregulation in edited tumor cells not only releases the PD‐1/PD‐L1 brake to improve the cancer killing capability of CD8+ T cells, but also enhances antitumor immune responses of immune cells. This provides a facile strategy to reverse tumor immunosuppression and to restore immunosurveillance and activate anti‐tumor immunity.

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“…The second format is delivering the elements of mRNA and sgRNA, with mRNA being converted into Cas9 nucleases via the process of translation in the cytoplasm. The last format of CRISPR/Cas9 delivery is RNP, the Cas9 protein and sgRNA complex that shows the advantages of its safety and low off‐target effects . The Cas9 nucleases generated by plasmid DNA are relatively stable and of low cost; however, plasmid DNA also has the potential to express the CRISPR/Cas9 elements persistently, which greatly enhances the potential to generate off‐target effects at undesired genome sites and sometimes even causes genetic mutations.…”

Section: Format Of Crispr/cas9 Deliverymentioning

confidence: 99%

“…The last format of CRISPR/Cas9 delivery is RNP, the Cas9 protein and sgRNA complex that shows the advantages of its safety and low off-target effects. 69 The Cas9 nucleases generated by plasmid DNA are relatively stable and of low cost; however, plasmid DNA also has the potential to express the CRISPR/Cas9 elements persistently, which greatly enhances the potential to generate off-target effects at undesired genome sites and sometimes even causes genetic mutations. By contrast, the delivery of mRNA and proteins represents a safe mode and shows strong activity to modify genes to sufficiently generate geneediting effects; yet their relatively short half-life well circumvents the limitations of plasmid DNA.…”

Section: Format Of Crispr/cas9 Deliverymentioning

confidence: 99%

Delivery of CRISPR/Cas9 for therapeutic genome editing

Wan

Xin

et al. 2019

The Journal of Gene Medicine

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110

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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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Material solutions for delivery of CRISPR/Cas-based genome editing tools: Current status and future outlook

Cited by 98 publications

References 202 publications

An anionic, endosome-escaping polymer to potentiate intracellular delivery of cationic peptides, biomacromolecules, and nanoparticles

An anionic, endosome-escaping polymer to potentiate intracellular delivery of cationic peptides, biomacromolecules, and nanoparticles

Aptamer/Peptide‐Functionalized Genome‐Editing System for Effective Immune Restoration through Reversal of PD‐L1‐Mediated Cancer Immunosuppression

Delivery of CRISPR/Cas9 for therapeutic genome editing

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