Research Progress on Nanoparticles-Based CRISPR/Cas9 System for Targeted Therapy of Tumors
Abstract
:1. Introduction
2. CRISPR/Cas9 System
2.1. Delivery of CRISPR/Cas9 System
2.2. Design of NPs-Based CRISPR/Cas9 System
3. Kinds of NPs-Based CRISPR/Cas9 System
3.1. LNPs
3.2. PNPs
3.3. INPs
3.4. NPs of Other Structures
4. Applications of NPs-Based CRISPR/Cas9 System in Cancer Therapy
4.1. Gene Therapy
4.2. Chemotherapy
4.3. Immunotherapy
4.4. Other Therapy
5. Potentials of CRISPR/Cas9 in Oncology
5.1. Clinical Trials and CAR-T Therapy
5.2. Generation of Organoid Cancer Models
6. Future Perspective and Challenges
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Delivery Approaches | NPs Formulation | CRISPR/Cas9 Cargo | Efficiency | Application | Reference |
---|---|---|---|---|---|
LNPs | Cationic liposomes | Cas9 sgRNA complexes | 80% | in vitro and in vivo | [66] |
Cationic liposomes modified with R8-DGR | sgRNA | -- | in vitro and in vivo | [73] | |
Amino-ionizable lipid NPs | Cas9 mRNA and sgRNA | ~70% (aggressive orthotopic glioblastoma) ~80% (disseminated ovarian tumors) | in vitro and in vivo | [74] | |
SORT | Cas9 mRNA and sgRNA | 40% (epithelial cells) 65% (endothelial cells) 12% (B cells) 10% (T cells) 93% (hepatocytes) 20% (liver) 50% (lung) 30% (spleen) | in vitro and in vivo | [75] | |
iPhos | Cas9 mRNA and sgRNA | ~91% (hepatocytes) ~34% (lung endothelial cells) ~20% (lung epithelial cells) ~13% (lung immune cells) ~30% (splenic macrophages) 6% (Splenic B cells) | in vivo | [76] | |
pH-sensitive cationic liposomes | Cas9 mRNA and sgRNA | -- | in vitro and in vivo | [79] | |
HMME@Lip-Cas9 | RNP | 17.28% (HMME@Lip-Cas9) 58.77% (HMME@Lip-Cas9 + ultrasound) | in vitro and in vivo | [80] | |
PNPs | PEI-β-cyclodextrin cationic polymers | pDNA | 19.1% (HBB locus) 7% (RHBDF1 locus) | in vitro | [81] |
Poly lactic-co-glycolic acid (PLGA) NPs | pDNA | 95% (murine bone marrow derived macrophages) | in vitro | [83] | |
MDNP | pDNA | -- | in vitro and in vivo | [12] | |
Polyglutamic acid-modified NPs | Cas9 RNPs | ~2 fold increase | in vitro | [86] | |
INPs | SEHPA NPs | RNP | >60% (EGFR editing efficiency) | in vitro and in vivo | [88] |
LACP | RNP | 68% | in vitro and in vivo | [67] | |
PEI-coated magnetic Fe3O4 NPs | pDNA | 13% (with magnetic field) 10% (without magnetic field) | in vitro | [90] | |
NPs of other structures | LHNPs | Cas9 protein and minicircle gRNA | 1.3 times more efficiently than Lip2k | in vitro and in vivo | [92] |
DNA nanowires | Cas9 protein and sgRNA | 36% | in vitro and in vivo | [94] | |
Cas9 N3BPs | Cas9 sgRNA complexes | 26.7% (Target 1) 32.1% (GRIN2B) | in vitro and in vivo | [96] |
Identifier | Target Gene | Phase | Condition |
---|---|---|---|
NCT03057912 | HPV E6/E7 | I | Human Papillomavirus-Related Malignant Neoplasm |
NCT03164135 | CISH | I/II | Gastrointestinal Epithelial Cancer, Gastrointestinal Neoplasms |
NCT04976218 | TGF-β | I | Solid Tumor |
NCT04767308 | CD5 | I | Relapsed/Refractory Hematopoietic Malignancies |
NCT03545815 | PD-1, TCR | I | Solid Tumor, Adult |
NCT05066165 | WT1 | I/II | Acute Myeloid Leukemia |
NCT05309733 | CD33 | Leukemia, Myeloid, Acute | |
NCT03747965 | PD-1 | I | Solid Tumor, Adult |
NCT04035434 | CD19 | I | B-cell Malignancy Non-Hodgkin Lymphoma B-cell Lymphoma Adult B Cell ALL |
NCT04502446 | CD70 | I | T Cell Lymphoma |
NCT03081715 | PD-1 | -- | Esophageal Cancer |
NCT05037669 | CD19 | I | Acute Lymphoblastic Leukemia, Chronic Lymphocytic Leukemia, Non Hodgkin Lymphoma |
NCT04244656 | BCMA | I | Multiple Myeloma |
NCT04438083 | CD70 | I | Renal Cell Carcinoma |
NCT03166878 | CD19 | I/II | B Cell Leukemia, B Cell Lymphoma |
NCT03398967 | CD19/CD20/CD22 | I/II | B Cell Leukemia, B Cell Lymphoma |
NCT04557436 | CD52, TRAC | I | B Acute Lymphoblastic Leukemia |
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Nie, D.; Guo, T.; Yue, M.; Li, W.; Zong, X.; Zhu, Y.; Huang, J.; Lin, M. Research Progress on Nanoparticles-Based CRISPR/Cas9 System for Targeted Therapy of Tumors. Biomolecules 2022, 12, 1239. https://doi.org/10.3390/biom12091239
Nie D, Guo T, Yue M, Li W, Zong X, Zhu Y, Huang J, Lin M. Research Progress on Nanoparticles-Based CRISPR/Cas9 System for Targeted Therapy of Tumors. Biomolecules. 2022; 12(9):1239. https://doi.org/10.3390/biom12091239
Chicago/Turabian StyleNie, Dengyun, Ting Guo, Miao Yue, Wenya Li, Xinyu Zong, Yinxing Zhu, Junxing Huang, and Mei Lin. 2022. "Research Progress on Nanoparticles-Based CRISPR/Cas9 System for Targeted Therapy of Tumors" Biomolecules 12, no. 9: 1239. https://doi.org/10.3390/biom12091239