Epithelial cell -derived microvesicles: A safe delivery platform of CRISPR/Cas9 conferring synergistic anti-tumor effect with sorafenib

He, Cong; Ali, Doulathunnisa Jaffar; Xu, Han; Kumaravel, Subhashree; Si, Ke; Li, Yumin; Sun, Bo; Ma, Junqing; Zhang, Xiao

doi:10.1016/j.yexcr.2020.112040

Cited by 36 publications

(38 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As such, the safe and efficient intracellular delivery of CRISPR/Cas9 is critical for effective therapeutic genome editing. The study by He et al showed that the use of epithelial cell-derived microvesicles (MVS) as a carrier to deliver CRISPR/Cas9 components to cancer cells showed strong anticancer effects against xenograft tumors, and this may become a safe CRISPR/Cas9 delivery platform for cancer patients (143). Furthermore, the application of nanotechnology can maximize the advantages of using lncRNA in combination with immunotherapy.…”

Section: Potential Therapeutic Approaches Of Lncrna As Important Targetsmentioning

confidence: 99%

Long Non-Coding RNAs in the Tumor Immune Microenvironment: Biological Properties and Therapeutic Potential

Xia

et al. 2021

Front. Immunol.

View full text Add to dashboard Cite

Cancer immunotherapy (CIT) is considered a revolutionary advance in the fight against cancer. The complexity of the immune microenvironment determines the success or failure of CIT. Long non-coding RNA (lncRNA) is an extremely versatile molecule that can interact with RNA, DNA, or proteins to promote or inhibit the expression of protein-coding genes. LncRNAs are expressed in many different types of immune cells and regulate both innate and adaptive immunity. Recent studies have shown that the discovery of lncRNAs provides a novel perspective for studying the regulation of the tumor immune microenvironment (TIME). Tumor cells and the associated microenvironment can change to escape recognition and elimination by the immune system. LncRNA induces the formation of an immunosuppressive microenvironment through related pathways, thereby controlling the escape of tumors from immune surveillance and promoting the development of metastasis and drug resistance. Using lncRNA as a therapeutic target provides a strategy for studying and improving the efficacy of immunotherapy.

show abstract

Section: Potential Therapeutic Approaches Of Lncrna As Important Targetsmentioning

confidence: 99%

Long Non-Coding RNAs in the Tumor Immune Microenvironment: Biological Properties and Therapeutic Potential

Xia

et al. 2021

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…He et al [ 106 ] employed epithelial cell derived microvesicles (MVs) to transport CRISPR/Cas9 components into tumor cells. The MVs were isolated from HEK293 cells stably transfected with Cas9 and loaded with plasmids encoding for sgRNAs targeting the IQ-domain GTPase-activating proteins.…”

Section: Direct Exosome Engineering After Their Isolationmentioning

confidence: 99%

“…Uptake of the loaded MVs reduced the viability of HepG2 liver cancer cells in vitro and a synergistic effect was demonstrated for combinations with sorafenib, which is a multi-kinase inhibitor. A substantial anti-cancer effect was also observed in vivo in a HepG2 xenograft mouse model [ 106 ].…”

Section: Direct Exosome Engineering After Their Isolationmentioning

confidence: 99%

CRISPR/Cas9: Principle, Applications, and Delivery through Extracellular Vesicles

Horodecka

Duechler

2021

IJMS

View full text Add to dashboard Cite

The establishment of CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) technology for eukaryotic gene editing opened up new avenues not only for the analysis of gene function but also for therapeutic interventions. While the original methodology allowed for targeted gene disruption, recent technological advancements yielded a rich assortment of tools to modify genes and gene expression in various ways. Currently, clinical applications of this technology fell short of expectations mainly due to problems with the efficient and safe delivery of CRISPR/Cas9 components to living organisms. The targeted in vivo delivery of therapeutic nucleic acids and proteins remain technically challenging and further limitations emerge, for instance, by unwanted off-target effects, immune reactions, toxicity, or rapid degradation of the transfer vehicles. One approach that might overcome many of these limitations employs extracellular vesicles as intercellular delivery devices. In this review, we first introduce the CRISPR/Cas9 system and its latest advancements, outline major applications, and summarize the current state of the art technology using exosomes or microvesicles for transporting CRISPR/Cas9 constituents into eukaryotic cells.

show abstract

“…The potential of microvesicles as delivery systems for genome-editing components has been investigated in a hepatocellular carcinoma model [42]. In this example, vesicles were collected from Cas9-expressing HepG2 or HEK293 cells and electroporated with plasmid DNA encoding sgRNA specific for the IQ-domain GTPase-activating protein 1 (IQGAP1) gene.…”

Section: Microvesiclesmentioning

confidence: 99%

“…Even though tropism towards the cell of origin enhances accumulation of certain extracellular vesicles at their target site, most nanovesicles have broad selectivity for various tissues. It was previously shown that microvesicles generated from HEK293 cells, one of the most popular extracellular vesicle-producing cells, are broadly distributed throughout the body, an unexpected outcome given the intended tumor-targeting capability [42]. Therefore, because off-target effects are the most pressing concern with genome-editing technology, achieving precise targeting of specific cells while maintaining the inherent advantages of extracellular vesicles will be necessary for safe genome editing.…”

Section: Microvesiclesmentioning

confidence: 99%

Nanovesicle-Mediated Delivery Systems for CRISPR/Cas Genome Editing

Kim

et al. 2020

Pharmaceutics

View full text Add to dashboard Cite

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.

show abstract

Epithelial cell -derived microvesicles: A safe delivery platform of CRISPR/Cas9 conferring synergistic anti-tumor effect with sorafenib

Cited by 36 publications

References 31 publications

Long Non-Coding RNAs in the Tumor Immune Microenvironment: Biological Properties and Therapeutic Potential

Long Non-Coding RNAs in the Tumor Immune Microenvironment: Biological Properties and Therapeutic Potential

CRISPR/Cas9: Principle, Applications, and Delivery through Extracellular Vesicles

Nanovesicle-Mediated Delivery Systems for CRISPR/Cas Genome Editing

Contact Info

Product

Resources

About