Extracellular nanovesicles for packaging of CRISPR-Cas9 protein and sgRNA to induce therapeutic exon skipping

Gee, Peter; Lung, Mandy Siu Yu; Okuzaki, Yuya; Sasakawa, Nobuyuki; Iguchi, T.; Makita, Yukimasa; Hozumi, Hiroyuki; Miura, Yasutomo; Yang, Linghai; Iwasaki, Mio; Wang, Xiou H.; Waller, Matthew A.; Shirai, Nanako; Abe, Yasuko; Fujita, Yöko; Watanabe, Kei; Kagita, Akihiro; Iwabuchi, Kumiko A.; Yasuda, Masahiko; Xu, Huaigeng; Noda, Takeshi; Komano, Jun; Sakurai, Hiroyuki; Inukai, Naoto; Hotta, Akitsu

doi:10.1038/s41467-020-14957-y

Cited by 262 publications

(227 citation statements)

References 52 publications

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“…The system reached over 90% exon skipping efficiencies. This innovative technique, as in vivo experiments have demonstrated, seems to be promising for DMD genome editing therapy [86].…”

Section: Gene Therapymentioning

confidence: 94%

“…The investigations about the Duchenne disease have sustained important progress in order to reduce the probability of off-targets mutagenesis and immunogenicity, generally due to the prolonged expression of the CRISPR/Cas9. Very recently, Gee et al [86] have developed an extracellular nanovesicle-based ribonucleoprotein delivery system named NanoMEDIC. This is developed on chemical dimerization and viral RNA packaging signal to recruit Cas9 protein and sgRNA into nanovesicles [86].…”

Section: Gene Therapymentioning

confidence: 99%

“…Very recently, Gee et al [86] have developed an extracellular nanovesicle-based ribonucleoprotein delivery system named NanoMEDIC. This is developed on chemical dimerization and viral RNA packaging signal to recruit Cas9 protein and sgRNA into nanovesicles [86]. They have tested this device in different cell types, among others in skeletal muscle cells derived from DMD-hiPSCs.…”

Section: Gene Therapymentioning

confidence: 99%

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Application of CRISPR/Cas9 to human-induced pluripotent stem cells: from gene editing to drug discovery

et al. 2020

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Human-induced pluripotent stem cells (hiPSCs) and CRISPR/Cas9 gene editing system represent two instruments of basic and translational research, which both allow to acquire deep insight about the molecular bases of many diseases but also to develop pharmacological research. This review is focused to draw up the latest technique of gene editing applied on hiPSCs, exploiting some of the genetic manipulation directed to the discovery of innovative therapeutic strategies. There are many expediencies provided by the use of hiPSCs, which can represent a disease model clinically relevant and predictive, with a great potential if associated to CRISPR/Cas9 technology, a gene editing tool powered by ease and precision never seen before. Here, we describe the possible applications of CRISPR/Cas9 to hiPSCs: from drug development to drug screening and from gene therapy to the induction of the immunological response to specific virus infection, such as HIV and SARS-Cov-2.

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“…The system reached over 90% exon skipping efficiencies. This innovative technique, as in vivo experiments have demonstrated, seems to be promising for DMD genome editing therapy [86].…”

Section: Gene Therapymentioning

confidence: 94%

Section: Gene Therapymentioning

confidence: 99%

Section: Gene Therapymentioning

confidence: 99%

See 1 more Smart Citation

Application of CRISPR/Cas9 to human-induced pluripotent stem cells: from gene editing to drug discovery

et al. 2020

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Section: Extracellular Vesiclesmentioning

confidence: 99%

“…Genome-editing factors, packaged in engineered CRISPR/Cas9 complexes, can be enclosed in extracellular vesicles (EVs), for delivery to specific target cells [ 86 , 87 ]. EVs are composed of cellular constituents such as lipids, proteins, RNA, and DNA [ 86 , 88 ]. EVs may cross the blood–brain barrier, target cells in vivo, and protect their components from degradation in the circulatory system [ 87 , 89 ].…”

Section: Extracellular Vesiclesmentioning

confidence: 99%

Emerging Gene-Editing Modalities for Osteoarthritis

Tanikella

Hardy

Frahs

et al. 2020

IJMS

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Osteoarthritis (OA) is a pathological degenerative condition of the joints that is widely prevalent worldwide, resulting in significant pain, disability, and impaired quality of life. The diverse etiology and pathogenesis of OA can explain the paucity of viable preventive and disease-modifying strategies to counter it. Advances in genome-editing techniques may improve disease-modifying solutions by addressing inherited predisposing risk factors and the activity of inflammatory modulators. Recent progress on technologies such as CRISPR/Cas9 and cell-based genome-editing therapies targeting the genetic and epigenetic alternations in OA offer promising avenues for early diagnosis and the development of personalized therapies. The purpose of this literature review was to concisely summarize the genome-editing options against chronic degenerative joint conditions such as OA with a focus on the more recently emerging modalities, especially CRISPR/Cas9. Future advancements in novel genome-editing therapies may improve the efficacy of such targeted treatments.

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A Cancer Cell Membrane‐Derived Biomimetic Nanocarrier for Synergistic Photothermal/Gene Therapy by Efficient Delivery of CRISPR/Cas9 and Gold Nanorods

Huang

Zhou

Abbas

et al. 2022

Adv Healthcare Materials

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Bimodal synergistic therapy produces superadditive effect for enhanced therapeutic efficacy. However, how to efficiently and simultaneously deliver several kinds of therapeutic agents is still challenging. A cancer cell membrane‐derived nanocarrier (mCas9‐sGNRs) is proposed for synergistic photothermal/gene therapy (PTT/GT) by efficient delivery of clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR‐associated protein 9 (Cas9) and gold nanorods (GNRs). In this approach, Cas9 proteins can be efficiently loaded inside the cell membranes (mCas9) by electrostatic interactions. Similarly, single‐guide RNAs, which target survivin, can be loaded onto GNRs (sGNRs) through electrostatic interactions and encapsulated by mCas9. As a result, the nanodelivery systems present advantages in biocompatibility, homologous targeting capacity and loading efficiency of cargoes. In addition, significant antitumor effects is achieved by gene editing of survivin which induces anticancer activity and reduces heat tolerance of cancer cells caused by GNRs mediated PTT due to the downregulation of HSP70. These results indicate the nanotherapeutic platform leads to enhanced PTT/GT efficacy. Therefore, this work not only provides a general strategy to construct a versatile nanoplatform for loading and target delivery of several therapeutic cargos but will also be valuable for PTT/GT and other bimodal synergistic therapy.

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Extracellular nanovesicles for packaging of CRISPR-Cas9 protein and sgRNA to induce therapeutic exon skipping

Cited by 262 publications

References 52 publications

Application of CRISPR/Cas9 to human-induced pluripotent stem cells: from gene editing to drug discovery

Application of CRISPR/Cas9 to human-induced pluripotent stem cells: from gene editing to drug discovery

Emerging Gene-Editing Modalities for Osteoarthritis

A Cancer Cell Membrane‐Derived Biomimetic Nanocarrier for Synergistic Photothermal/Gene Therapy by Efficient Delivery of CRISPR/Cas9 and Gold Nanorods

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