Skip to main content
SpringerLink
Log in

Nanotechnology based CRISPR/Cas9 system delivery for genome editing: Progress and prospect

  • Review Article
  • Published:
Nano Research Aims and scope Submit manuscript

Abstract

The genome editing tool, clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system, has achieved successful therapeutic efficacy via precise modification of the genome and exceeded previous genome engineering methods owing to its versatility and simplicity. Rapid expansion in biomedical research has benefited from this newly emerged technique, such as genetic diseases treatment, cancer characterization, and plant improvement. However, the key challenge is efficient delivery of CRISPR components in vivo and nanotechnology plays an indispensable role in nonviral gene delivery. In this review, we will first briefly describe the mechanism and delivery strategies of CRISPR/Cas9 system. Furthermore, the past and current researches of nanoparticles based CRISPR/Cas9 system delivery for genome I editing will be highlighted. Finally, we will discuss the challenges and prospects of CRISPR/Cas9 system combined with nanotechnology I for clinical translation in the future.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Barrangou, R. The roles of CRISPR-Cas systems in adaptive immunity and beyond. Curr. Opin. Immunol. 2015, 32, 36–41.

    CAS  Google Scholar 

  2. Barrangou, R.; Fremaux, C; Deveau, H.; Richards, M.; Boyaval, P.; Moineau, S.; Romero, D. A.; Horvath, P. CRISPR provides acquired resistance against viruses in prokaryotes. Science 2007, 315, 1709–1712.

    CAS  Google Scholar 

  3. Zhang, F.; Wen, Y.; Guo, X. CRISPR/Cas9 for genome editing: Progress, implications and challenges. Hum. Mol. Genet. 2014, 23, R40-R46.

    CAS  Google Scholar 

  4. Atmos, J. Diagram of the possible mechanism for CRISPR. Photo: Wikipedia. 2009.

    Google Scholar 

  5. Mojica, F. J. M.; Díez-Villaseñor, C; Soria, E.; Juez, G. Biological significance of a family of regularly spaced repeats in the genomes of Archaea, Bacteria and mitochondria. Mol. Microbiol. 2000, 36, 244–246.

    CAS  Google Scholar 

  6. Deltcheva, E.; Chylinski, K.; Sharma, C. M.; Gonzales, K.; Chao, Y. J.; Pirzada, Z. A.; Eckert, M. R.; Vogel, J.; Charpentier, E. CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III. Nature 2011, 77, 602–607.

    Google Scholar 

  7. Jinek, M.; Chylinski, K.; Fonfara, I.; Hauer, M.; Doudna, J. A.; Charpentier, E. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 2012, 337, 816–821.

    CAS  Google Scholar 

  8. Cong, L.; Ran, F. A; Cox, D.; Lin, S. L.; Barretto, R.; Habib, N; Hsu, P. D.; Wu, X. B.; Jiang, W. Y.; Marraffini, L. et al. Multiplex genome engineering using CRISPR/Cas systems. Science 2013, 339, 819–823.

    CAS  Google Scholar 

  9. Wu, Y. X.; Zhou, H.; Fan, X. Y.; Zhang, Y.; Zhang, M.; Wang, Y. H.; Xie, Z. F.; Bai, M. Z.; Yin, Q.; Liang, D. et al. Correction of a genetic disease by CRISPR-Cas9-mediated gene editing in mouse spermatogonial stem cells. Cell Res. 2015, 25, 67–79.

    CAS  Google Scholar 

  10. Cho, S. W.; Kim, S.; Kim, J. M.; Kim, J. S. Targeted genome engineering in human cells with the Cas9 RNA-guided endonuclease. Nat. Biotechnol. 2013, 31, 230–232.

    CAS  Google Scholar 

  11. Bikard, D.; Euler, C. W.; Jiang, W. Y.; Nussenzweig, P. M.; Goldberg, G. W.; Duportet, X.; Fischetti, V. A; Marraffini, L. A. Exploiting CRISPR-Cas nucleases to produce sequence- specific antimicrobials. Nat. Biotechnol. 2014, 32, 1146–1150.

    CAS  Google Scholar 

  12. Hwang, W. Y.; Fu, Y. F.; Reyon, D.; Maeder, M. L.; Tsai, S. Q.; Sander, J. D.; Peterson, R. T.; Yeh, J. R.; Joung, J. K. Efficient genome editing in zebrafish using a CRISPR-Cas system. Nat. Biotechnol. 2013, 31, 227–229.

    CAS  Google Scholar 

  13. Nekrasov, V.; Staskawicz, B.; Weigel, D.; Jones, J. D. G.; Kamoun, S. Targeted mutagenesis in the model plant Nicotiana benthamiana using Cas9 RNA-guided endonuclease. Nat. Biotechnol. 2013, 31, 691–693.

    CAS  Google Scholar 

  14. Wu, Y. X.; Liang, D.; Wang, Y. H; Bai, M. Z.; Tang, W.; Bao, S. M.; Yan, Z. Q.; Li, D. S.; Li, J. S. Correction of a genetic disease in mouse via use of CRISPR-Cas9. Cell Stem Cell 2013,13, 659–662.

    CAS  Google Scholar 

  15. Long, C. Z.; McAnally, J. R.; Shelton, J. M.; Mireault, A. A.; Bassel- Duby, R.; Olson, E. N. Prevention of muscular dystrophy in mice by CRISPR/ Cas9-mediated editing of germline DNA. Science 2014, 345, 1184–1188.

    CAS  Google Scholar 

  16. Schwank, G.; Koo, B. K; Sasselli, V.; Dekkers, J. F.; Heo, I.; Demircan, T.; Sasaki, N.; Boymans, S.; Cuppen, E.; van der Ent, C. K. et al. Functional repair of CFTR by CRISPR/Cas9 in intestinal stem cell organoids of cystic fibrosis patients. Cell Stem Cell 2013, 13, 653–658.

    CAS  Google Scholar 

  17. Yin, H.; Xue, W.; Chen, S. D.; Bogorad, R. L.; Benedetti, E.; Grompe, M.; Koteliansky, V.; Sharp, P. A.; Jacks, T.; Anderson, D. G. Genome editing with Cas9 in adult mice corrects a disease mutation and phenotype. Nat. Biotechnol. 2014, 32, 551–553.

    CAS  Google Scholar 

  18. Yin, H.; Song, C. Q.; Dorkin, J. R.; Zhu, L. J.; Li, Y. X.; Wu, Q. Q.; Park, A.; Yang, J.; Suresh, S.; Bizhanova, A. et al. Therapeutic genome editing by combined viral and non-viral delivery of CRISPR system components in vivo. Nat. Biotechnol. 2016, 34, 328–333.

    CAS  Google Scholar 

  19. Ran, F. A.; Cong, L.; Yan, W. X.; Scott, D. A; Gootenberg, J. S.; Kriz, A. J.; Zetsche, B.; Shalem, O.; Wu, X. B.; Makarova, K. S. et al. In vivo genome editing using Staphylococcus aureus Cas9. Nature 2015, 520, 186–191.

    CAS  Google Scholar 

  20. Antal, C. E.; Hudson, A. M.; Kang, E.; Zanca, C; Wirth, C; Stephenson, N. L.; Trotter, E. W.; Gallegos, L. L.; Miller, C. J.; Furnari, F. B. et al. Cancer-associated protein kinase C mutations reveal kinase’s role as tumor suppressor. Cell 2015, 160, 489–502.

    CAS  Google Scholar 

  21. Ye, L.; Wang, J. M.; Beyer, A. I.; Teque, F.; Cradick, T. J.; Qi, Z. X.; Chang, J. C; Bao, G.; Muench, M. O.; Yu, J. W. et al. Seamless modification of wild-type induced pluripotent stem cells to the natural CCR5A32 mutation confers resistance to HIV infection. Proc Natl Acad Sci USA 2014, 777, 9591–9596.

    Google Scholar 

  22. Zhen, S.; Hua, L.; Liu, Y. H; Gao, L. C; Fu, J.; Wan, D. Y.; Dong, L. H; Song, H. F.; Gao, X. Harnessing the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated Cas9 system to disrupt the hepatitis B virus. Gene Ther. 2015, 22, 404–412.

    CAS  Google Scholar 

  23. Kennedy, E. M.; Kornepati, A. V. R.; Goldstein, M.; Bogerd, H. P.; Poling, B. C; Whisnant, A. W.; Kastan, M. B.; Cullen, B. R. Inactivation of the human papillomavirus E6 or E7 gene in cervical carcinoma cells by using a bacterial CRISPR/Cas RNA-guided endonuclease. J. Virol. 2014, 88, 11965–11972.

    Google Scholar 

  24. Gilbert, L. A.; Larson, M. H; Morsut, L.; Liu, Z. R.; Brar, G. A.; Torres, S. E.; Stern- Ginossar, N.; Brandman, O.; Whitehead, E. H; Doudna, J. A. et al. CRISPR-mediated modular RNA-guided regulation of transcription in eukaryotes. Cell 2013, 154, 442–451.

    CAS  Google Scholar 

  25. Komor, A. C; Badran, A. H; Liu, D. R. CRISPR-based technologies for the manipulation of eukaryotic genomes. Cell 2017, 168, 20–36.

    CAS  Google Scholar 

  26. Chen, B. H.; Gilbert, L. A.; Cimini, B. A.; Schnitzbauer, J.; Zhang, W.; Li, G. W.; Park, J.; Blackburn, E. H; Weissman, J. S.; Qi, L. S. et al. Dynamic imaging of genomic loci in living human cells by an optimized CRISPR/Cas system. Cell 2013, 755, 1479–1491.

    Google Scholar 

  27. Fujita, T.; Fujii, H. Efficient isolation of specific genomic regions and identification of associated proteins by engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP) using CRISPR. Biochem. Biophys. Res. Commun. 2013, 439, 132–136.

    CAS  Google Scholar 

  28. Zetsche, B.; Gootenberg, J. S.; Abudayyeh, O. O.; Slaymaker, I. M.; Makarova, K. S.; Essletzbichler, P.; Volz, S. E.; Joung, J.; van der Oost, J.; Regev, A. et al. Cpfl is a single RNA-guided endonuclease of a class 2 CRISPR-Cas system. Cell 2015, 163, 759–771.

    CAS  Google Scholar 

  29. Li, B.; Zhao, W. Y; Luo, X.; Zhang, X. R; Li, C. L.; Zeng, C. X.; Dong, Y. Z. Engineering CRISPR-Cpfl crRNAs and mRNAs to maximize genome editing efficiency. Nat. Biomed. Eng. 2017, 7, 0066.

    Google Scholar 

  30. Abudayyeh, O. O.; Gootenberg, J. S.; Essletzbichler, P.; Han, S.; Joung, J.; Belanto, J. J.; Verdine, V.; Cox, D. B. T; Kellner, M. J.; Regev, A. et al. RNAtargeting with CRISPR-Casl3. Nature 2017, 550, 280–284.

    Google Scholar 

  31. Chen, J. S.; Ma, E. B.; Harrington, L. B.; Da Costa, M.; Tian, X. R.; Palefsky, J. M.; Doudna, J. A. CRISPR-Casl2a target binding unleashes indiscriminate single-stranded DNase activity. Science 2018, 360, 436–139.

    CAS  Google Scholar 

  32. Liu, C; Zhang, L.; Liu, H.; Cheng, K. Delivery strategies of the CRISPR- Cas9 gene-editing system for therapeutic applications. J. Control. Release 2017, 266, 17–26.

    CAS  Google Scholar 

  33. Grimm, D.; Kay, M. A. From virus evolution to vector revolution: Use of naturally occurring serotypes of adeno-associated virus (AAV) as novel vectors for human gene therapy. Curr. Gene Ther. 2003, 3, 281–304.

    CAS  Google Scholar 

  34. Niidome, T.; Huang, L. Gene therapy progress and prospects: Nonviral vectors. Gene Ther. 2002, 9, 1647–1652.

    CAS  Google Scholar 

  35. Makarova, K. S.; Wolf, Y. I.; Alkhnbashi, O. S.; Costa, F.; Shah, S. A.; Saunders, S. J.; Barrangou, R.; Brouns, S. J. J.; Charpentier, E.; Haft, D. H. et al. An updated evolutionary classification of CRISPR-Cas systems. Nat. Rev. Microbiol. 2015, 13, 722–736.

    CAS  Google Scholar 

  36. Leenay, R. T.; Maksimchuk, K. R.; Slotkowski, R. A.; Agrawal, R. N; Gomaa, A. A.; Briner, A. E.; Barrangou, R.; Beisel, C. L. Identifying and visualizing functional PAM diversity across CRISPR-Cas systems. Mol. Cell 2016, 62, 137–147.

    CAS  Google Scholar 

  37. Shmakov, S.; Smargon, A.; Scott, D.; Cox, D.; Pyzocha, N; Yan, W.; Abudayyeh, O. O.; Gootenberg, J. S.; Makarova, K. S.; Wolf, Y. I. et al. Diversity and evolution of class 2 CRISPR-Cas systems. Nat. Rev. Microbiol. 2017, 75, 169–182.

    Google Scholar 

  38. Mohanraju, P.; Makarova, K. S.; Zetsche, B.; Zhang, F.; Koonin, E. V.; van der Oost, J. Diverse evolutionary roots and mechanistic variations of the CRISPR-Cas systems. Science 2016, 353, aad5147.

    Google Scholar 

  39. Garneau, J. E.; Dupuis, M. E.; Villion, M.; Romero, D. A.; Barrangou, R.; Boyaval, P.; Fremaux, C; Horvath, P.; Magadan, A. H.; Moineau, S. The CRISPR/Cas bacterial immune system cleaves bacteriophage and plasmid DNA. Nature 2010, 468, 61–11.

    Google Scholar 

  40. Makarova, K. S.; Haft, D. H; Barrangou, R.; Brouns, S. J. J.; Charpentier, E.; Horvath, P.; Moineau, S.; Mojica, F. J. M.; Wolf, Y. I.; Yakunin, A. F. et al. Evolution and classification of the CRISPR-Cas systems. Nat. Rev. Microbiol. 2011, 9, 467–477.

    CAS  Google Scholar 

  41. Marraffini, L. A.; Sontheimer, E. J. CRISPR interference limits horizontal gene transfer in staphylococci by targeting DNA. Science 2008, 322, 1843–1845.

    CAS  Google Scholar 

  42. Brouns, S. J. J; Jore, M. M.; Lundgren, M.; Westra, E. R.; Slijkhuis, R J. H; Snijders, A. P. L.; Dickman, M. J.; Makarova, K. S.; Koonin, E. V.; van der Oost, J. Small CRISPR RNAs guide antiviral defense in prokaryotes. Science 2008, 321, 960–964.

    CAS  Google Scholar 

  43. Perez, E. E.; Wang, J. B.; Miller, J. C; Jouvenot, Y.; Kim, K. A.; Liu, O; Wang, N; Lee, G.; Bartsevich, V. V.; Lee, Y. L. et al. Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleases. Nat. Biotechnol. 2008, 26, 808–816.

    CAS  Google Scholar 

  44. Chen, F. Q.; Pruett- Miller, S. M.; Huang, Y. P.; Gjoka, M.; Duda, K.; Taunton, J.; Collingwood, T. N.; Frodin, M.; Davis, G. D. High-frequency genome editing using ssDNA oligonucleotides with zinc-finger nucleases. Nat. Methods 2011, 8, 753–755.

    CAS  Google Scholar 

  45. Saleh-Gohari, N; Helleday, T. Conservative homologous recombination preferentially repairs DNA double-strand breaks in the S phase of the cell cycle in human cells. Nucleic Acids Res. 2004, 32, 3683–3688.

    CAS  Google Scholar 

  46. Jones, C. H; Chen, C. K; Ravikrishnan, A.; Rane, S.; Pfeifer, B. A. Overcoming nonviral gene delivery barriers: Perspective and future. Mol. Pharm. 2013, 10, 4082–4098.

    CAS  Google Scholar 

  47. Kamimura, K; Suda, T.; Zhang, G. S.; Liu, D. X. Advances in gene delivery systems. Pharm. Med. 2011, 25, 293–306.

    Google Scholar 

  48. Chira, S.; Gulei, D.; Hajitou, A; Zimta, A. A.; Cordelier, P.; Berindan- Neagoe, I. CRISPR/Cas9: Transcending the reality of genome editing. Mol. Ther. Nucleic Acids 2017, 7, 211–222.

    Google Scholar 

  49. Ran, F. A.; Hsu, P. D.; Wright, J.; Agarwala, V.; Scott, D. A.; Zhang, F. Genome engineering using the CRISPR-Cas9 system. Nat. Protoc. 2013, 8, 2281–2308.

    CAS  Google Scholar 

  50. Niu, Y. Y.; Shen, B.; Cui, Y. Q.; Chen, Y. C; Wang, J. Y.; Wang, L.; Kang, Y.; Zhao, X. Y.; Si, W.; Li, W. et al. Generation of gene-modified cynomolgus monkey via Cas9/RNA-mediated gene targeting in one-cell embryos. Cell 2014, 756, 836–843.

    Google Scholar 

  51. Zuris, J. A.; Thompson, D. B.; Shu, Y. L.; Guilinger, J. P.; Bessen, J. L.; Hu, J. H; Maeder, M. L.; Joung, J. K; Chen, Z. Y.; Liu, D. R. Cationic lipid-mediated delivery of proteins enables efficient protein-based genome editing in vitro and in vivo. Nat. Biotechnol. 2015, 33, 73–80.

    CAS  Google Scholar 

  52. Hughes, T. S.; Langer, S. J.; Virtanen, S. I.; Chavez, R. A.; Watkins, L. R.; Milligan, E. D.; Leinwand, L. A. Immunogenicity of intrathecal plasmid gene delivery: Cytokine release and effects on transgene expression. J. GeneMed. 2009, 77, 782–790.

    Google Scholar 

  53. Hemmi, H; Takeuchi, O; Kawai, T.; Kaisho, T.; Sato, S.; Sanjo, H; Matsumoto, M.; Hoshino, K; Wagner, H; Takeda, K. et al. A toll-like receptor recognizes bacterial DNA. Nature 2000, 408, 740–745.

    CAS  Google Scholar 

  54. Shen, B.; Zhang, W. S.; Zhang, J.; Zhou, J. K; Wang, J. Y.; Chen, L.; Wang, L.; Hodgkins, A.; Iyer, V.; Huang, X. X. et al. Efficient genome modification by CRISPR-Cas9 nickase with minimal off-target effects. Nat.Methods 2014, 77, 399–102.

    Google Scholar 

  55. Chang, N. N; Sun, C. H.; Gao, L.; Zhu, D.; Xu, X. F.; Zhu, X. J.; Xiong, J. W.; Xi, J. J. Genome editing with RNA-guided Cas9 nuclease in zebrafish embryos. Cell Res. 2013, 23, 465–472.

    CAS  Google Scholar 

  56. Wu, Y. X.; Liang, D.; Wang, Y. H; Bai, M. Z.; Tang, W.; Bao, S. M.; Yan, Z. Q.; Li, D. S.; Li, J. S. Correction of a genetic disease in mouse via use of CRISPR-Cas9. Cell Stem Cell 2013, 13, 659–662.

    CAS  Google Scholar 

  57. Ran, F. A.; Hsu, P. D.; Lin, C. Y.; Gootenberg, J. S.; Konermann, S.; Trevino, A. E.; Scott, D. A.; Inoue, A; Matoba, S.; Zhang, Y. et al. Double nicking by RNA-guided CRISPR Cas9 for enhanced genome editing specificity. Cell 2013, 1 54, 1380–1389.

    Google Scholar 

  58. Schumann, K.; Lin, S.; Boyer, E.; Simeonov, D. R.; Subramaniam, M.; Gate, R. E.; Haliburton, G. E.; Ye, C. J.; Bluestone, J. A.; Doudna, J. A. et al. Generation of knock-in primary human T cells using Cas9 ribonucleoproteins. Proc Natl Acad Sci USA 2015, 772, 10437–10442.

    Google Scholar 

  59. Peer, D.; Karp, J. M.; Hong, S.; Farokhzad, O. C; Margalit, R.; Langer, R. Nanocarriers as an emerging platform for cancer therapy. Nat. Nanotechnol. 2007, 2, 751–760.

    CAS  Google Scholar 

  60. Chew, W. L.; Tabebordbar, M.; Cheng, J. K. W.; Mali, P.; Wu, E. Y.; Ng, A. H. M.; Zhu, K. X.; Wagers, A. J.; Church, G. M. A multifunctional AAV-CRISPR-Cas9 and its host response. Nat. Methods 2016, 13, 868–874.

    CAS  Google Scholar 

  61. Ryu, N; Kim, M. A.; Park, D.; Lee, B.; Kim, Y R.; Kim, K. H.; Baek, J. I.; Ki, W. J.; Lee, K. Y; Kim, U. K. Effective PEI-mediated delivery of CRISPR-Cas9 complex for targeted gene therapy. Nanomedicine 2018, 14, 2095–2102.

    CAS  Google Scholar 

  62. Zhang, Z.; Wan, T.; Chen, Y. X.; Chen, Y; Sun, H. W.; Cao, T. Q.; Zhou, S. Y; Tang, G P.; Wu, C. B.; Ping, Y. et al. Cationic polymer-mediated CRISPR/Cas9 plasmid delivery for genome editing. Macromol. Rapid. Commun. 2019, 40, 1800068.

    Google Scholar 

  63. Sun, W. J.; Ji, W. Y; Hall, J. M.; Hu, Q. Y; Wang, C; Beisel, C. L.; Gu, Z. Self-assembled DNA nanoclews for the efficient delivery of CRISPR-Cas9 for genome editing. Angew. Chem., Int. Ed. 2015, 54, 12029–12033.

    CAS  Google Scholar 

  64. Liu, Q.; Zhao, K; Wang, C; Zhang, Z. Z.; Zheng, C. X.; Zhao, Y; Zheng, Y. D.; Liu, C. Y; An, Y. L.; Shi, L. Q. et al. Multistage delivery nanoparticle facilitates efficient CRISPR/dCas9 activation and tumor growth suppression in vivo. Adv. Sci. 2019, 6, 1801423.

    Google Scholar 

  65. Kang, Y. K; Kwon, K; Ryu, J. S.; Lee, H. N.; Park, C; Chung, H. J. Nonviral genome editing based on a polymer-derivatized CRISPR nanocomplex for targeting bacterial pathogens and antibiotic resistance. Bioconjug. Chem. 2017, 28, 957–967.

    CAS  Google Scholar 

  66. Smith, T. T.; Stephan, S. B.; Moffett, H. E; McKnight, L. E.; Ji, W. H.; Reiman, D.; Bonagofski, E.; Wohlfahrt, M. E.; Pillai, S. P. S.; Stephan, M. T In situ programming of leukaemia-specific T cells using synthetic DNA nanocarriers. Nat. Nanotechnol. 2017, 12, 813–820.

    CAS  Google Scholar 

  67. Moffett, H. E; Coon, M. E.; Radtke, S.; Stephan, S. B.; McKnight, L.; Lambert, A.; Stoddard, B. L.; Kiem, H. P.; Stephan, M. T. Hit-and-run programming of therapeutic cytoreagents using mRNA nanocarriers. Nat. Commun. 2017, 8, 389.

  68. Zhu, D.; Shen, H; Tan, S. W.; Hu, Z.; Wang, L. M.; Yu, L.; Tian, X.; Ding, W. C; Ren, C; Gao, C. et al. Nanoparticles Based on poly (p-Amino Ester) and HPV16-targeting CRISPR/shRNA as potential drugs for HPV16-related cervical malignancy. Mo/. Ther. 2018, 26, 2443–2455.

    CAS  Google Scholar 

  69. Liu, Y; Chen, D.; Li, J. L.; Xia, D. N.; Yu, M. R.; Tao, J. S.; Zhang, X. X.; Li, L.; Gan, Y. NPC1 L1 -targeted cholesterol-grafted poly(p-amino ester)/pDNA complexes for oral gene delivery. Adv. Healthc. Mater. 2019, 8, 1800934.

    Google Scholar 

  70. Liu, S.; Jia, H. T; Yang, J. X.; Pan, J. P.; Liang, H. Y; Zeng, L. H; Zhou, H; Chen, J. T; Guo, T. Y. Zinc coordinated cationic polymers break up the paradox between low molecular weight and high transfection efficacy. Biomacromolecules 2018, 19, 4270–1276.

    CAS  Google Scholar 

  71. Chen, G J.; Ma, B.; Wang, Y. Y; Gong, S. Q. Auniversal GSH-responsive nanoplatform for the delivery of DNA, mRNA, and Cas9/sgRNA ribonucleoprotein. ACSAppl. Mater. Interfaces 2018, 10, 18515–18523.

    CAS  Google Scholar 

  72. Luo, Y. L.; Xu, C. F.; Li, H. J.; Cao, Z. T.; Liu, J.; Wang, J. L.; Du, X. J.; Yang, X. Z.; Gu, Z.; Wang, J. Macrophage-specific in vivo gene editing using cationic lipid-assisted polymeric nanoparticles. ACS Nana 2018, 12, 994–1005.

    CAS  Google Scholar 

  73. Xu, C. F.; Lu, Z. D.; Luo, Y. L.; Liu, Y.; Cao, Z. T.; Shen, S.; Li, H. J.; Liu, J.; Chen, K. G.; Chen, Z. Y. et al. Targeting of NLRP3 inflammasome with gene editing for the amelioration of inflammatory diseases. Nat. Commun. 2018, 9, 4092.

  74. Liu, Y.; Cao, Z. T.; Xu, C. F.; Lu, Z. D.; Luo, Y. L.; Wang, J. Optimization of lipid-assisted nanoparticle for disturbing neutrophils-related inflammation. Biomaterials 2018, 172, 92–104.

    CAS  Google Scholar 

  75. Liu, Y.; Zhao, G.; Xu, C. F.; Luo, Y. L.; Lu, Z. D.; Wang, J. Systemic delivery of CRISPR/Cas9 with PEG-PLGA nanoparticles for chronic myeloid leukemia targeted therapy. Biomater. Sci. 2018, 6, 1592–1603.

    CAS  Google Scholar 

  76. Li, M.; Fan, Y. N; Chen, Z. Y.; Luo, Y. L.; Wang, Y. C; Lian, Z. X.; Xu, C. F.; Wang, J. Optimized nanoparticle-mediated delivery of CRISPR-Cas9 system for B cell intervention. NanoRes. 2018, 11, 6270–6282.

    CAS  Google Scholar 

  77. Wang, M.; Zuris, J. A.; Meng, F. T.; Rees, H.; Sun, S.; Deng, P.; Han, Y.; Gao, X.; Pouli, D.; Wu, Q. et al. Efficient delivery of genome-editing proteins using bioreducible lipid nanoparticles. Proc Nati Acad Sci USA 2016, 113, 2868–2873.

    CAS  Google Scholar 

  78. Finn, J. D.; Smith, A. R.; Patel, M. C; Shaw, L.; Youniss, M. R.; van Heteren, J.; Dirstine, T.; Ciullo, C; Lescarbeau, R.; Seitzer, J. et al. A single administration of CRISPR/Cas9 lipid nanoparticles achieves robust and persistent in vivo genome editing. Cell Rep. 2018, 22, 2227–2235.

    CAS  Google Scholar 

  79. Zhang, L. M.; Wang, P.; Feng, Q.; Wang, N. X.; Chen, Z. T.; Huang, Y. Y.; Zheng, W. F.; Jiang, X. Y. Lipid nanoparticle-mediated efficient delivery of CRISPR/Cas9 for tumor therapy. NPGAsiaMat. 2017, 9, e441.

    CAS  Google Scholar 

  80. Chen, Z. M.; Liu, F. Y.; Chen, Y. K; Liu, J.; Wang, X. Y.; Chen, A. T.; Deng, G.; Zhang, H. Y.; Liu, J.; Hong, Z. Y. et al. Targeted delivery of CRISPR/Cas9-mediated cancer gene therapy via liposome-templated hydrogel nanoparticles. Adv. Fund. Mater. 2017, 27, 1703036.

    Google Scholar 

  81. Jiang, C; Mei, M.; Li, B.; Zhu, X. R.; Zu, W. H; Tian, Y. J.; Wang, Q. N; Guo, Y; Dong, Y. Z.; Tan, X. Anon-viral CRISPR/Cas9 delivery system for therapeutically targeting HBV DNA and pcsk9 in vivo. Cell Res. 2017, 27, 440–143.

    CAS  Google Scholar 

  82. He, Z. Y.; Zhang, Y. G; Yang, Y. H; Ma, C. C; Wang, P.; Du, W.; Li, L.; Xiang, R.; Song, X. R.; Zhao, X. et al. Q. In vivo ovarian cancer gene therapy using CRISPR-Cas9. Hum. Gene Ther. 2018, 29, 223–233.

    CAS  Google Scholar 

  83. Liang, C; Li, F. F.; Wang, L. Y.; Zhang, Z. K.; Wang, C; He, B.; Li, J.; Chen, Z. H.; Shaikh, A. B.; Liu, J. et al. Tumor cell-targeted delivery of CRISPR/Cas9 by aptamer-functionalized lipopolymer for therapeutic genome editing of VEGFA in osteosarcoma. Biomaterials 2017,147, 68–85.

    CAS  Google Scholar 

  84. Mircetic, J.; Steinebrunner, I.; Ding, L.; Fei, J. F.; Bogdanova, A.; Drechsel, D.; Buchholz, F. Purified Cas9 fusion proteins for advanced genome manipulation. Small Methods 2017, 1, 1600052.

    Google Scholar 

  85. Mout, R.; Ray, M.; Tonga, G. Y.; Lee, Y. W.; Tay, T.; Sasaki, K.; Rotello, V. M. Direct cytosolic delivery of CRISPR/Cas9-ribonucleoprotein for efficient gene editing. ACS Nana 2017, 11, 2452–2458.

    CAS  Google Scholar 

  86. Lee, K.; Conboy, M.; Park, H. M.; Jiang, F. G.; Kim, H. J.; Dewitt, M. A.; Mackley, V. A.; Chang, K; Rao, A.; Skinner, C. et al. Nanoparticle delivery of Cas9 ribonucleoprotein and donor DNA in vivo induces homology-directed DNA repair. Nat. Biomed. Eng. 2017, 1, 889–901.

    CAS  Google Scholar 

  87. Wang, P.; Zhang, L M.; Zheng, W. F.; Cong, L. M.; Guo, Z. R.; Xie, Y. Z. Y.; Wang, L.; Tang, R. B.; Feng, Q.; Hamada, Y. et al. Thermo-triggered release of CRISPR-Cas9 system by lipid-encapsulated gold nanoparticles for tumor therapy. Angew. Chem., Int. Ed. 2018, 57, 1491–1496.

    CAS  Google Scholar 

  88. Ramakrishna, S.; Kwaku Dad, A. B.; Beloor, J.; Gopalappa, R.; Lee, S. K.; Kim, H. Gene disruption by cell-penetrating peptide-mediated delivery of Cas9 protein and guide RNA. Genome Res. 2014, 24, 1020–1027.

    CAS  Google Scholar 

  89. Wang, H. X.; Song, Z. Y.; Lao, Y. H.; Xu, X.; Gong, J.; Cheng, D.; Chakraborty, S.; Park, J. S.; Li, M. Q.; Huang, D. T. et al. Nonviral gene editing via CRISPR/Cas9 delivery by membrane-disruptive and endosomolytic helical polypeptide. Proc Natl Acad Sci USA 2018, 115, 4903–4908.

    CAS  Google Scholar 

  90. Kim, S. M.; Yang, Y.; Oh, S. J.; Hong, Y.; Seo, M.; Jang, M. Cancer-derived exosomes as a delivery platform of CRISPR/Cas9 confer cancer cell tropism-dependent targeting. J. Control. Release 2017, 266, 8–16.

    CAS  Google Scholar 

  91. Li, Z. L.; Zhou, X. Y.; Wei, M. Y.; Gao, X. T.; Zhao, L. B.; Shi, R J; Sun, W. Q.; Duan, Y. Y.; Yang, G. D.; Yuan, L. J. In vitro and in vivo RNA inhibition by CD9-HuR functionalized exosomes encapsulated with miRNA or CRISPR/dCas9.NanoLett. 2019, 19, 19–28.

    CAS  Google Scholar 

  92. Lin, Y.; Wu, J. H.; Gu, W. H; Huang, Y. L.; Tong, Z. C; Huang, L. J.; Tan, J. L. Exosome-liposome hybrid nanoparticles deliver CRISPR/Cas9 system in MSCs. ADV Sci. 2018, 5, 1700611.

    Google Scholar 

  93. Usman, W. M.; Pham, T. C; Kwok, Y. Y.; Vu, L. T.; Ma, V.; Peng, B. Y.; Chan, Y. S.; Wei, L. K.; Chin, S. M.; Azad, A. et al. Efficient RNA drug delivery using red blood cell extracellular vesicles. Nat. Commun. 2018, 9, 2359.

  94. Li, L.; Song, L. J.; Liu, X. W.; Yang, X.; Li, X.; He, T.; Wang, N; Yang, S. L. X.; Yu, C; Yin, T. et al. Artificial virus delivers CRISPR-Cas9 system for genome editing of cells in mice. ACSNano 2017, 11, 95–111.

    CAS  Google Scholar 

  95. Yue, H. H.; Zhou, X. M.; Cheng, M.; Xing, D. Graphene oxide-mediated Cas9/sgRNA delivery for efficient genome editing. Nanoscale 2018, 10, 1063–1071.

    CAS  Google Scholar 

  96. Zhou, W. H; Cui, H. D.; Ying, L. M.; Yu, X. F. Enhanced cytosolic delivery and release of CRISPR/Cas9 by black phosphorus nanosheets for genome editing. Angew. Chem., Int. Ed. 2018, 57, 10268–10272.

    CAS  Google Scholar 

  97. Alsaiari, S. K; Patil, S.; Alyami, M.; Alamoudi, K. O; Aleisa, F. A.; Merzaban, J. S.; Li, M.; Khashab, N. M. Endosomal escape and delivery of CRISPR/Cas9 genome editing machinery enabled by nanoscale zeolitic imidazolate framework. J.Am. Chem. Soc. 2018, 140, 143–146.

    CAS  Google Scholar 

  98. Yang, X. T; Tang, Q.; Jiang, Y; Zhang, M. N; Wang, M.; Mao, L. Q. Nanoscale ATP-responsive zeolitic imidazole framework-90 as a general platform for cytosolic protein delivery and genome editing. J. Am. Chem. Soc. 2019, 141, 3782–3786.

    CAS  Google Scholar 

  99. Mout, R.; Ray, M.; Lee, Y. W.; Scaletti, R; Rotello, V. M. In vivo delivery of CRISPR/Cas9 for therapeutic gene editing: Progress and challenges. Bioconjug. Chem. 2017, 28, 880–884.

    CAS  Google Scholar 

  100. Wang, H. X.; Li, M. Q.; Lee, C. M.; Chakraborty, S.; Kim, H. W.; Bao, G; Leong, K. M. CRISPR/Cas9-based genome editing for disease modeling and therapy: Challenges and opportunities for nonviral delivery. Chem. Rev. 2017, 117, 9874–9906.

    CAS  Google Scholar 

  101. Hendel, A.; Bak, R. O.; Clark, J. T.; Kennedy, A. B.; Ryan, D. K; Roy, S.; Steinfeld, I.; Lunstad, B. D.; Kaiser, R J.; Wilkens, A. B. et al. Chemically modified guide RNAs enhance CRISPR-Cas genome editing in human primary cells. Nat. Biotechnol. 2015, 33, 985–989.

    CAS  Google Scholar 

  102. Rahdar, M.; McMahon, M. A; Prakash, T. P.; Swayze, R. E.; Bennett, C. R; Cleveland, D. W. Synthetic CRISPR RNA-Cas9-guided genome editing in human cells. Proc Natl Acad Sci USA 2015, 112, E7110-E7117.

  103. Zhang, J. J.; Mao, R; Niu, G; Peng, L.; Lang, L X.; Li, R; Ying, H. Y; Wu, H. W.; Pan, B. J.; Zhu, Z. H. et al. 68Ga-BBN-RGD PRT/CT for GRPR and integrin avp3 imaging in patients with breast cancer. Theranostics 2018, 8, 1121–1130.

    CAS  Google Scholar 

  104. Amin, M.; Mansourian, M.; Koning, G A.; Badiee, A.; Jaafari, M. R.; Ten Hagen, T. L. M. Development of a novel cyclic RGD peptide for multiple targeting approaches of liposomes to tumor region. J. Control. Release 2015, 220, 308–315.

    CAS  Google Scholar 

  105. Jinek, M.; Jiang, R G; Taylor, D. W.; Sternberg, S. H.; Kaya, E.; Ma, E. B.; Anders, C; Hauer, M.; Zhou, K. H.; Lin, S. et al. Structures of Cas9 endonucleases reveal RNA-mediated conformational activation. Science 2014, 343, 1247997.

    Google Scholar 

  106. Dobrovolskaia, M. A.; Aggarwal, P.; Hall, J. B.; McNeil, S. E. Preclinical studies to understand nanoparticle interaction with the immune system and its potential effects on nanoparticle biodistribution. Mol. Pharm. 2008, 5, 487–495.

    CAS  Google Scholar 

  107. Aggarwal, P.; Hall, J. B.; McLeland, C. B.; Dobrovolskaia, M. A.; McNeil, S. E. Nanoparticle interaction with plasma proteins as it relates to particle biodistribution, biocompatibility and therapeutic efficacy. Adv. DrugDeliv. Rev. 2009, 61, 428–437.

    CAS  Google Scholar 

  108. Kobayashi, H; Watanabe, R.; Choyke, P. L. Improving conventional enhanced permeability and retention (EPR) effects; What is the appropriate target? Theranostics 2014, 4, 81–89.

    CAS  Google Scholar 

  109. Lu, M. Q.; Ho, Y. P.; Grigsby, C. L.; Nawaz, A. A.; Leong, K. W.; Huang, T. J. Three-dimensional hydrodynamic focusing method for polyplex synthesis. ACS Nana 2014, 8, 332–339.

    CAS  Google Scholar 

  110. Li, L.; Hu, S.; Chen, X. Y Non-viral delivery systems for CRISPR/Cas9-based genome editing: Challenges and opportunities. Biomaterials 2018, 171, 207–218.

    CAS  Google Scholar 

  111. Strecker, J.; Jones, S.; Koopal, B.; Schmid- Burgk, J.; Zetsche, B.; Gao, L. Y; Makarova, K. S.; Koonin, E. V.; Zhang, F. Engineering of CRISPR- Casl2b for human genome editing. Nat. Commun. 2019, 10, 212.

  112. Wan, T; Niu, D.; Wu, C. B.; Xu, F. J; Church, G; Ping, Y Material solutions for delivery of CRISPR/Cas-based genome editing tools: Current status and future outlook. Mater. Today 2019, 26, 40–66.

    CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Natural Science Foundation of China (Nos. 81673374 and 81872810), Wuhan Science and Technology Plan for Applied Fundamental Research (No. 2017060201010146), and Fundamental Research Funds for the Central Universities (No. 2018KFYYXJJ019).

Author information

Author notes

  1. Huan Deng and Wei Huang contributed equally to this work.

Authors and Affiliations

  1. Tongji School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Huan Deng & Zhiping Zhang

  2. Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Wei Huang

  3. National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan, 430030, China

    Zhiping Zhang

  4. Hubei Engineering Research Center for Novel Drug Delivery System, Huazhong University of Science and Technology, Wuhan, 430030, China

    Zhiping Zhang

Authors
  1. Huan Deng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wei Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zhiping Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zhiping Zhang.

Ethics declarations

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Deng, H., Huang, W. & Zhang, Z. Nanotechnology based CRISPR/Cas9 system delivery for genome editing: Progress and prospect. Nano Res. 12, 2437–2450 (2019). https://doi.org/10.1007/s12274-019-2465-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12274-019-2465-x

Keywords

Search

Navigation