Advancements in CRISPR/Cas systems for disease treatment

Figures

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  Figure 1. A milestone in the evolution of the CRISPR/Cas9 system. Created by processon.com.

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  Figure 2. Mechanism of antiviral resistance in CRISPR/Cas9 system. Reprinted with the permission from Ref. 1. Copyright@2023 The American Association for the Advancement of Science.

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  Figure 3. Schematic illustration of various Cas9-based gene editing tools. (A) The first generation of CRISPR/Cas9. Reprinted with the permission from Ref. 10. Copyright@2023, The Authors; (B) Cas9 nickase (Cas9n), a variant of Cas9, usually with only one nucleic acid endonuclease structural domain. Reprinted with the permission from Ref. 10. Copyright@2023, The Authors; (C) Cas12a and (D) Cas13a. Reprinted with the permission from Ref. 10. Copyright@2023, The Authors; (E) Cas9-based CRISPRi system by engineered Cas protein and (F) the CRISPRa system. Reprinted with the permission from Ref. 9. Copyright@2023 Springer Nature; (G) The base editing and prime editing enable the interchange of all bases. Reprinted with the permission from Ref. 68. Copyright@2023 The Authors.

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  Figure 4. Schematic illustration of viral vector-mediated CRISPR/Cas9-based gene therapy. (A) Strategies of viral vector delivered CRISPR/Cas9 in vivo and ex vivo. Reprinted with the permission from Ref. 234. Copyright@2021, The Authors; (B) sgRNA library was packed by AAV to screen and identify functional suppressors in glioblastoma. Reprinted with the permission from Ref. 251. Copyright@2017 Springer Nature.

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  Figure 5. The development of selective organs targeting LNP via optimizing the composition of lipids, utilizing the various lipids results in the specific accumulation in the liver, spleen, and lung respectively. Reprinted with the permission from Ref. 300. Copyright@2020 Springer Nature.

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  Figure 6. Representative examples of PNP delivered CRISPR/Cas9 system. (A) Synthesis of PF for highly efficient delivery CRISPR/Cas9 for gene editing in vivo and in vitro. Reprinted with the permission from Ref. 308. Copyright@2017, American Chemical Society; (B) Multistage responsive “core–shell” PNP for KO immune checkpoint PD-L1 and CD47 simultaneously. Reprinted with the permission from Ref. 93. Copyright@2020 John Wiley and Sons; (C) Reprinted with the permission from Ref. 20. Copyright@2021 The Authors and (D) PNP were used to deliver the dCas9-based CRISPRa system to activate the endogenous gene. Reprinted with the permission from Ref. 309. Copyright@2023, The Authors.

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  Figure 7. Representative examples of biomimetic, EVs and inorganic nanoparticles delivered CRISPR/Cas9 system. (A) The preparations of ONCOTECH, CM-expressed pMHC-Ⅰ can be identified by T cells and delivered to tumor cells for gene editing. Reprinted with the permission from Ref. 337. Copyright@2024 Springer Nature; (B) Engineered exosomes for delivery of CRISPRi targeting TAM towards M1 polarization. Reprinted with the permission from Ref. 348. Copyright@2023 John Wiley and Sons; (C) AuNPs-mediated PTT was used to enhance gene editing efficiency. Reprinted with the permission from Ref. 299. Copyright@2018 John Wiley and Sons.