New Therapeutics for Extracellular Vesicles: Delivering CRISPR for Cancer Treatment
Abstract
:1. Introduction
2. CRISPR Function and Cellular Delivery
2.1. Origin and Biological Functions of CRISPR/Cas9
2.2. Established Methods for CRISPR/Cas9 Delivery
2.2.1. Physical and Nonviral Approaches
2.2.2. Viral Vectors
3. Extracellular Vesicle Biology and the Therapeutic Potential
3.1. Extracellular Vesicles Biology and Subclassification
3.2. EV Therapeutics for Cancer Treatment
4. EV-Mediated CRISPR/Cas9 Delivery for Cancer Therapy
4.1. EV-CRISPR Administration Targeting Various Types of Cancers
4.2. Tactics Used to Fabricate EV-CRISPR Vectors
4.2.1. Plasmid DNA Encapsulation for EV-CRISPR/Cas9
4.2.2. Cas9 mRNA Sorting for EV-CRISPR/Cas9
4.2.3. Cas9 Protein or RNP Acquirement for EV-CRISPR/Cas9
5. Discussion and Clinical Prospects
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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EV Source | CRISPR Form | EV Loading Method | Target Gene | Target Cell/Animal | Major Outcome | Ref. |
---|---|---|---|---|---|---|
HEK293T | Plasmid | Electroporation | MYC | Raji (B lymphocytes), Nalm6 (B cell precursor leukemia cells) | Induced cell apoptosis, inhibited tumor size | [103] |
HEK293T | Plasmid | Electroporation | IQGAP1 | HuH7 (liver cancer cells) | Induced cell apoptosis, in vitro only | [104] |
SKOV3 | Plasmid | Electroporation | PARP-1 | SKOV3 (ovarian cancer cell), SKOV3-grafted mice | Inhibited cell proliferation, induced apoptosis, inhibited tumor growth | [105] |
HEK293T | Plasmid | Exo-Fect™ Exosome Transfection Kit (SBI) | KrasG12D | KPC689 (pancreatic tumor cell), KPC689-grafted mice | Suppressed cell proliferation, attenuated tumor progression | [106] |
HEK293T | Plasmid | EV/liposome fusion | Runx2, CTNNB1 | Murine MSC | Suppressed protein expression | [107] |
RBCs | Cas9 mRNA + sgRNA | Electroporation | miR-125b | MOLM13 (acute myeloid leukemia cells) | Suppressed miR-125b expression | [101] |
HEK293T, AML12 (mouse hepatocytes) | Cas9 mRNA + sgRNA | CD9-HuR + Cas9 mRNA with ARE motif | C/ebpa | Adipogenic stem cells, mice | Suppressed C/ebpa expression | [108] |
HEK293T | Cas9 RNP | Sonication, freeze–thaw cycling | WNT10B | HepG2, HepG2-grafted BALB/c nude mice | Reduced cell viability, inhibited tumor progression | [109] |
MDA-MB-231 | Cas9 RNP | EV/cationic lipid nanoparticle (PULSin®) fusion | Not examined | Raw 264.7 (macrophages), MDA-MB-231 (breast cancer cells) | Unaffected cell uptake efficiency, negligible cytotoxicity | [110] |
HepAD38, HuH7, Vero, CHO, Hela | Cas9 RNP | Cas9 overexpression | HBV DNA, HPV DNA | HepAD38 (HBV-expressive liver cells), HuH7 (liver cancer cells), Hela (cervical cancer cells) | Cut HBV or HPV DNA in cells | [111] |
HEK293T | Cas9 RNP | CD63-GFP + Cas9-nanobody | The stop element | A549Stop-DsRed (lung cancer cells) | DsRed expression | [112] |
HEK293T | Cas9 RNP | CD63-COM + sgRNA-com | DMD intron 50, intron 51, exon 53 | DMD reporter cell, del52hDMD/mdx mice | Multiplex cleavage of target genes | [113] |
HEK293T | Cas9 RNP | Cas9 myristoylation | EGFP | EGFP stably expressed HEK293T | Downregulated EGFP expression | [114] |
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Yan, B.; Liang, Y. New Therapeutics for Extracellular Vesicles: Delivering CRISPR for Cancer Treatment. Int. J. Mol. Sci. 2022, 23, 15758. https://doi.org/10.3390/ijms232415758
Yan B, Liang Y. New Therapeutics for Extracellular Vesicles: Delivering CRISPR for Cancer Treatment. International Journal of Molecular Sciences. 2022; 23(24):15758. https://doi.org/10.3390/ijms232415758
Chicago/Turabian StyleYan, Biying, and Yaxuan Liang. 2022. "New Therapeutics for Extracellular Vesicles: Delivering CRISPR for Cancer Treatment" International Journal of Molecular Sciences 23, no. 24: 15758. https://doi.org/10.3390/ijms232415758