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Polymer-Mediated Delivery of CRISPR-Cas9 Genome-Editing Therapeutics for CNS Disease

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Engineering Biomaterials for Neural Applications

Abstract

CRISPR-Cas9 (clustered, regularly interspaced, short palindromic repeats-associated protein 9) refers to a site-specific method of gene manipulation at the genome level. CRISPR was first discovered in bacteria and archaea as small segments of DNA inserted into CRISPR arrays, which are recognized as an adaptive immune system mechanism to defend against viruses and plasmids. Since the pioneering work on CRISPR sequences in the 1980s, CRISPR-Cas9, which was adapted from the naturally occurring system, has been widely used in gene function research and genetic engineering. CRISPR-based genome editing made a huge leap forward in 2013 when studies on efficient gene manipulation in mammalian cells were reported. CRISPR-Cas9 editing is highly versatile because of its simple operation, specificity, and high efficiency in modifying target genes. Theoretically, any genome sequence can be edited by this system, which has advanced applications ranging from research in basic biology to biotechnology and medicine.

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References

  • Baliou, S., Adamaki, M., Kyriakopoulos, A. M., Spandidos, D. A., Panayiotidis, M., Christodoulou, I., et al. (2018). CRISPR therapeutic tools for complex genetic disorders and cancer. International Journal of Oncology, 53(2), 443–468.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Barrangou, R., Fremaux, C., Deveau, H., Richards, M., Boyaval, P., Moineau, S., et al. (2007). CRISPR provides acquired resistance against viruses in prokaryotes. Science, 315(5819), 1709–1712.

    Article  CAS  PubMed  Google Scholar 

  • Boussif, O., Lezoualc’h, F., Zanta, M. A., Mergny, M. D., Scherman, D., Demeneix, B., et al. (1995). A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: Polyethylenimine. Proceedings of the National Academy of Sciences, 92(16), 7297–7301.

    Article  CAS  Google Scholar 

  • Brouns, S. J., Jore, M. M., Lundgren, M., Westra, E. R., Slijkhuis, R. J., Snijders, A. P., et al. (2008). Small CRISPR RNAs guide antiviral defense in prokaryotes. Science, 321(5891), 960–964.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chang, N., Sun, C., Gao, L., Zhu, D., Xu, X., Zhu, X., et al. (2013). Genome editing with RNA-guided Cas9 nuclease in zebrafish embryos. Cell Research, 23(4), 465–472.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen, Z., Liu, F., Chen, Y., Liu, J., Wang, X., Chen, A. T., et al. (2017). Targeted delivery of CRISPR/Cas9-mediated cancer gene therapy via liposome-templated hydrogel nanoparticles. Advanced Functional Materials, 27(46), 1703036.

    Article  PubMed  PubMed Central  Google Scholar 

  • Chen, G., Ma, B., Wang, Y., & Gong, S. (2018). A universal GSH-responsive nanoplatform for the delivery of DNA, mRNA, and Cas9/sgRNA ribonucleoprotein. ACS Applied Materials & Interfaces, 10(22), 18515–18523.

    Article  CAS  Google Scholar 

  • Chen, G., Abdeen, A. A., Wang, Y., Shahi, P. K., Robertson, S., Xie, R., et al. (2019). A biodegradable nanocapsule delivers a Cas9 ribonucleoprotein complex for in vivo genome editing. Nature Nanotechnology, 14(10), 974–980.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cheng, W.-J., Chen, L.-C., Ho, H.-O., Lin, H.-L., & Sheu, M.-T. (2018). Stearyl polyethylenimine complexed with plasmids as the core of human serum albumin nanoparticles noncovalently bound to CRISPR/Cas9 plasmids or siRNA for disrupting or silencing PD-L1 expression for immunotherapy. International Journal of Nanomedicine, 13, 7079.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chou, S.-J., Yang, P., Ban, Q., Yang, Y.-P., Wang, M.-L., Chien, C.-S., et al. (2020). Dual supramolecular nanoparticle vectors enable CRISPR/Cas9-mediated knockin of retinoschisin 1 gene – A potential nonviral therapeutic solution for X-linked juvenile retinoschisis. Advanced Science, 7(10), 1903432.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cong, L., Ran, F. A., Cox, D., Lin, S., Barretto, R., Habib, N., et al. (2013). Multiplex genome engineering using CRISPR/Cas systems. Science, 339(6121), 819–823.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Deng, H., Huang, W., & Zhang, Z. (2019). Nanotechnology based CRISPR/Cas9 system delivery for genome editing: Progress and prospect. Nano Research, 12(10), 2437–2450.

    Article  CAS  Google Scholar 

  • Deng, S., Li, X., Liu, S., Chen, J., Li, M., Chew, S. Y., et al. (2020). Codelivery of CRISPR-Cas9 and chlorin e6 for spatially controlled tumor-specific gene editing with synergistic drug effects. Science Advances, 6(29), eabb4005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ding, F., Huang, X., Gao, X., Xie, M., Pan, G., Li, Q., et al. (2019). A non-cationic nucleic acid nanogel for the delivery of the CRISPR/Cas9 gene editing tool. Nanoscale, 11(37), 17211–17215.

    Article  CAS  PubMed  Google Scholar 

  • Fu, Y., Foden, J. A., Khayter, C., Maeder, M. L., Reyon, D., Joung, J. K., et al. (2013). High-frequency off-target mutagenesis induced by CRISPR-Cas nucleases in human cells. Nature Biotechnology, 31(9), 822–826.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gao, Y., Huang, J.-Y., O’Keeffe Ahern, J., Cutlar, L., Zhou, D., Lin, F.-H., et al. (2016). Highly branched poly(β-amino esters) for non-viral gene delivery: High transfection efficiency and low toxicity achieved by increasing molecular weight. Biomacromolecules, 17(11), 3640–3647.

    Article  CAS  PubMed  Google Scholar 

  • Guan, L., Han, Y., Yang, C., Lu, S., Du, J., Li, H., et al. (2021). CRISPR-Cas9-mediated gene therapy in neurological disorders. Molecular Neurobiology, 59(2), 968–982.

    Article  PubMed  Google Scholar 

  • Han, H. A., Pang, J. K. S., & Soh, B.-S. (2020). Mitigating off-target effects in CRISPR/Cas9-mediated in vivo gene editing. Journal of Molecular Medicine, 98(5), 615–632.

    Article  CAS  PubMed  Google Scholar 

  • He, X.-Y., Liu, B.-Y., Peng, Y., Zhuo, R.-X., & Cheng, S.-X. (2018). Multifunctional vector for delivery of genome editing plasmid targeting β-catenin to remodulate cancer cell properties. ACS Applied Materials & Interfaces, 11(1), 226–237.

    Article  Google Scholar 

  • He, X., Long, Q., Zeng, Z., Yang, L., Tang, Y., & Feng, X. (2019). Simple and efficient targeted intracellular protein delivery with self-assembled nanovehicles for effective cancer therapy. Advanced Functional Materials, 29(50), 1906187.

    Article  CAS  Google Scholar 

  • Horvath, P., & Barrangou, R. (2010). CRISPR/Cas, the immune system of bacteria and archaea. Science, 327(5962), 167–170.

    Article  CAS  PubMed  Google Scholar 

  • Hsu, P. D., Scott, D. A., Weinstein, J. A., Ran, F. A., Konermann, S., Agarwala, V., et al. (2013). DNA targeting specificity of RNA-guided Cas9 nucleases. Nature Biotechnology, 31(9), 827–832.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hughes, T. S., Langer, S. J., Virtanen, S. I., Chavez, R. A., Watkins, L. R., Milligan, E. D., et al. (2009). Immunogenicity of intrathecal plasmid gene delivery: Cytokine release and effects on transgene expression. The Journal of Gene Medicine, 11(9), 782–790.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Iqbal, S., Yasin, M. N., & Sheardown, H. (2019). Engineering of targeted nanoparticles by using self-assembled biointegrated block copolymers. In Surface modification of nanoparticles for targeted drug delivery (pp. 451–466). Springer.

    Chapter  Google Scholar 

  • Iqbal, S., Blenner, M., Alexander-Bryant, A., & Larsen, J. (2020). Polymersomes for therapeutic delivery of protein and nucleic acid macromolecules: From design to therapeutic applications. Biomacromolecules, 21(4), 1327–1350.

    Article  CAS  PubMed  Google Scholar 

  • Ishino, Y., Shinagawa, H., Makino, K., Amemura, M., & Nakata, A. (1987). Nucleotide sequence of the iap gene, responsible for alkaline phosphatase isozyme conversion in Escherichia coli, and identification of the gene product. Journal of Bacteriology, 169(12), 5429–5433.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jiang, C., Mei, M., Li, B., Zhu, X., Zu, W., Tian, Y., et al. (2017). A non-viral CRISPR/Cas9 delivery system for therapeutically targeting HBV DNA and pcsk9 in vivo. Cell Research, 27(3), 440–443.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jinek, M., Chylinski, K., Fonfara, I., Hauer, M., Doudna, J. A., & Charpentier, E. (2012). A programmable dual-RNA–guided DNA endonuclease in adaptive bacterial immunity. Science, 337(6096), 816–821.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jinek, M., East, A., Cheng, A., Lin, S., Ma, E., & Doudna, J. (2013). RNA-programmed genome editing in human cells. elife, 2, e00471.

    Article  PubMed  PubMed Central  Google Scholar 

  • Jinek, M., Jiang, F., Taylor, D. W., Sternberg, S. H., Kaya, E., Ma, E., et al. (2014). Structures of Cas9 endonucleases reveal RNA-mediated conformational activation. Science, 343, 6176.

    Article  Google Scholar 

  • Kang, Y. K., Kwon, K., Ryu, J. S., Lee, H. N., Park, C., & Chung, H. J. (2017). Nonviral genome editing based on a polymer-derivatized CRISPR nanocomplex for targeting bacterial pathogens and antibiotic resistance. Bioconjugate Chemistry, 28(4), 957–967.

    Article  CAS  PubMed  Google Scholar 

  • Kantor, A., McClements, M. E., & MacLaren, R. E. (2020). CRISPR-Cas9 DNA base-editing and prime-editing. International Journal of Molecular Sciences, 21(17), 6240.

    Article  CAS  PubMed Central  Google Scholar 

  • Kanduri, V., LaVigne, D., & Larsen, J. (2021). Current advances toward the encapsulation of Cas9. ACS Macro Letters, 10, 1576–1589. https://doi.org/10.1021/acsmacrolett.1c00538

  • Kelly, J. M., Gross, A. L., Martin, D. R., & Byrne, M. E. (2017). Polyethylene glycol-b-poly (lactic acid) polymersomes as vehicles for enzyme replacement therapy. Nanomedicine, 12(23), 2591–2606.

    Article  CAS  PubMed  Google Scholar 

  • Kempe, K., & Nicolazzo, J. A. (2021). Biodegradable polymeric nanoparticles for brain-targeted drug delivery. In Nanomedicines for brain drug delivery (pp. 1–27). Springer.

    Google Scholar 

  • Kim, S., Kim, D., Cho, S. W., Kim, J., & Kim, J.-S. (2014). Highly efficient RNA-guided genome editing in human cells via delivery of purified Cas9 ribonucleoproteins. Genome Research, 24(6), 1012–1019.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim, H. J., Ogura, S., Otabe, T., Kamegawa, R., Sato, M., Kataoka, K., et al. (2019). Fine-tuning of hydrophobicity in amphiphilic polyaspartamide derivatives for rapid and transient expression of messenger RNA directed toward genome engineering in brain. ACS Central Science, 5(11), 1866–1875.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kleinstiver, B. P., Pattanayak, V., Prew, M. S., Tsai, S. Q., Nguyen, N. T., Zheng, Z., et al. (2016). High-fidelity CRISPR–Cas9 nucleases with no detectable genome-wide off-target effects. Nature, 529(7587), 490–495.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kretzmann, J. A., Ho, D., Evans, C. W., Plani-Lam, J. H. C., Garcia-Bloj, B., Mohamed, A. E., et al. (2017). Synthetically controlling dendrimer flexibility improves delivery of large plasmid DNA. Chemical Science, 8(4), 2923–2930.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • L’Amoreaux, N., Ali, A., Iqbal, S., & Larsen, J. (2020). Persistent prolate polymersomes for enhanced co-delivery of hydrophilic and hydrophobic drugs. Nanotechnology, 31(17), 175103.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lao, Y.-H., Li, M., Gao, M. A., Shao, D., Chi, C.-W., Huang, D., et al. (2018). HPV oncogene manipulation using nonvirally delivered CRISPR/Cas9 or natronobacterium gregoryi argonaute. Advanced Science, 5(7), 1700540.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lee, K., Conboy, M., Park, H. M., Jiang, F., Kim, H. J., Dewitt, M. A., et al. (2017). Nanoparticle delivery of Cas9 ribonucleoprotein and donor DNA in vivo induces homology-directed DNA repair. Nature Biomedical Engineering, 1(11), 889–901.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee, B., Lee, K., Panda, S., Gonzales-Rojas, R., Chong, A., Bugay, V., et al. (2018). Nanoparticle delivery of CRISPR into the brain rescues a mouse model of fragile X syndrome from exaggerated repetitive behaviours. Nature Biomedical Engineering, 2(7), 497–507.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li, L., Song, L., Liu, X., Yang, X., Li, X., He, T., et al. (2017). Artificial virus delivers CRISPR-Cas9 system for genome editing of cells in mice. ACS Nano, 11(1), 95–111.

    Article  CAS  PubMed  Google Scholar 

  • Li, L., Yang, Z., Zhu, S., He, L., Fan, W., Tang, W., et al. (2019). A rationally designed semiconducting polymer brush for NIR-II imaging-guided light-triggered remote control of CRISPR/Cas9 genome editing. Advanced Materials, 31(21), 1901187.

    Article  Google Scholar 

  • Liang, X., Potter, J., Kumar, S., Zou, Y., Quintanilla, R., Sridharan, M., et al. (2015). Rapid and highly efficient mammalian cell engineering via Cas9 protein transfection. Journal of Biotechnology, 208, 44–53.

    Article  CAS  PubMed  Google Scholar 

  • Liang, C., Li, F., Wang, L., Zhang, Z.-K., Wang, C., He, B., et al. (2017). Tumor cell-targeted delivery of CRISPR/Cas9 by aptamer-functionalized lipopolymer for therapeutic genome editing of VEGFA in osteosarcoma. Biomaterials, 147, 68–85.

    Article  CAS  PubMed  Google Scholar 

  • Lin, Y.-X., Wang, Y., Blake, S., Yu, M., Mei, L., Wang, H., et al. (2020). RNA nanotechnology-mediated cancer immunotherapy. Theranostics, 10(1), 281.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lino, C. A., Harper, J. C., Carney, J. P., & Timlin, J. A. (2018). Delivering CRISPR: A review of the challenges and approaches. Drug Delivery, 25(1), 1234–1257.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu, B.-Y., He, X.-Y., Xu, C., Xu, L., Ai, S.-L., Cheng, S.-X., et al. (2018a). A dual-targeting delivery system for effective genome editing and in situ detecting related protein expression in edited cells. Biomacromolecules, 19(7), 2957–2968.

    Article  CAS  PubMed  Google Scholar 

  • Liu, B.-Y., He, X.-Y., Zhuo, R.-X., & Cheng, S.-X. (2018b). Tumor targeted genome editing mediated by a multi-functional gene vector for regulating cell behaviors. Journal of Controlled Release, 291, 90–98.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Liu, Q., Zhao, K., Wang, C., Zhang, Z., Zheng, C., Zhao, Y., et al. (2019a). Multistage delivery nanoparticle facilitates efficient CRISPR/dCas9 activation and tumor growth suppression in vivo. Advanced Science, 6(1), 1801423.

    Article  PubMed  Google Scholar 

  • Liu, C., Wan, T., Wang, H., Zhang, S., Ping, Y., & Cheng, Y. (2019b). A boronic acid–rich dendrimer with robust and unprecedented efficiency for cytosolic protein delivery and CRISPR-Cas9 gene editing. Science Advances, 5(6), eaaw8922.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu, Q., Cai, J., Zheng, Y., Tan, Y., Wang, Y., Zhang, Z., et al. (2019c). NanoRNP overcomes tumor heterogeneity in cancer treatment. Nano Letters, 19(11), 7662–7672.

    Article  CAS  PubMed  Google Scholar 

  • Luo, Y.-L., Xu, C.-F., Li, H.-J., Cao, Z.-T., Liu, J., Wang, J.-L., et al. (2018). Macrophage-specific in vivo gene editing using cationic lipid-assisted polymeric nanoparticles. ACS Nano, 12(2), 994–1005.

    Article  CAS  PubMed  Google Scholar 

  • Lyu, Y., He, S., Li, J., Jiang, Y., Sun, H., Miao, Y., et al. (2019). A photolabile semiconducting polymer nanotransducer for near-infrared regulation of CRISPR/Cas9 gene editing. Angewandte Chemie, International Edition, 58(50), 18197–18201.

    Article  CAS  Google Scholar 

  • MacLaughlin, F. C., Mumper, R. J., Wang, J., Tagliaferri, J. M., Gill, I., Hinchcliffe, M., et al. (1998). Chitosan and depolymerized chitosan oligomers as condensing carriers for in vivo plasmid delivery. Journal of Controlled Release, 56(1–3), 259–272.

    Article  CAS  PubMed  Google Scholar 

  • Makarova, K. S., Haft, D. H., Barrangou, R., Brouns, S. J., Charpentier, E., Horvath, P., et al. (2011). Evolution and classification of the CRISPR–Cas systems. Nature Reviews. Microbiology, 9(6), 467–477.

    Article  CAS  PubMed  Google Scholar 

  • Mali, P., Yang, L., Esvelt, K. M., Aach, J., Guell, M., DiCarlo, J. E., et al. (2013). RNA-guided human genome engineering via Cas9. Science, 339(6121), 823–826.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Misra, M. K., Damotte, V., & Hollenbach, J. A. (2018). The immunogenetics of neurological disease. Immunology, 153(4), 399–414.

    Article  CAS  PubMed  Google Scholar 

  • Monteys, A. M., Ebanks, S. A., Keiser, M. S., & Davidson, B. L. (2017). CRISPR/Cas9 editing of the mutant huntingtin allele in vitro and in vivo. Molecular Therapy, 25(1), 12–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Naeem, M., Majeed, S., Hoque, M. Z., & Ahmad, I. (2020). Latest developed strategies to minimize the off-target effects in CRISPR-Cas-mediated genome editing. Cell, 9(7), 1608.

    Article  CAS  Google Scholar 

  • Niu, Y., Shen, B., Cui, Y., Chen, Y., Wang, J., Wang, L., et al. (2014). Generation of gene-modified cynomolgus monkey via Cas9/RNA-mediated gene targeting in one-cell embryos. Cell, 156(4), 836–843.

    Article  CAS  PubMed  Google Scholar 

  • Elzoghby, A. O., Abd-Elwakil, M. M., Abd-Elsalam, K., Elsayed, M. T., Hashem, Y., & Mohamed, O. (2016). Natural polymeric nanoparticles for brain-targeting: Implications on drug and gene delivery. Current Pharmaceutical Design, 22(22), 3305–3323.

    Article  CAS  PubMed  Google Scholar 

  • Patel, T., Zhou, J., Piepmeier, J. M., & Saltzman, W. M. (2012). Polymeric nanoparticles for drug delivery to the central nervous system. Advanced Drug Delivery Reviews, 64(7), 701–705.

    Article  CAS  PubMed  Google Scholar 

  • Pena, S. A., Iyengar, R., Eshraghi, R. S., Bencie, N., Mittal, J., Aljohani, A., et al. (2020). Gene therapy for neurological disorders: Challenges and recent advancements. Journal of Drug Targeting, 28(2), 111–128.

    Article  CAS  PubMed  Google Scholar 

  • Peviani, M., Capasso Palmiero, U., Cecere, F., Milazzo, R., Moscatelli, D., & Biffi, A. (2019). Biodegradable polymeric nanoparticles administered in the cerebrospinal fluid: Brain biodistribution, preferential internalization in microglia and implications for cell-selective drug release. Biomaterials, 209, 25–40.

    Article  CAS  PubMed  Google Scholar 

  • Qi, Y., Song, H., Xiao, H., Cheng, G., Yu, B., & Xu, F.-J. (2018). Fluorinated acid-labile branched hydroxyl-rich nanosystems for flexible and robust delivery of plasmids. Small, 14(42), 1803061.

    Article  Google Scholar 

  • Qiao, J., Sun, W., Lin, S., Jin, R., Ma, L., & Liu, Y. (2019). Cytosolic delivery of CRISPR/Cas9 ribonucleoproteins for genome editing using chitosan-coated red fluorescent protein. Chemical Communications, 55(32), 4707–4710.

    Article  CAS  PubMed  Google Scholar 

  • Ran, F. A., Cong, L., Yan, W. X., Scott, D. A., Gootenberg, J. S., Kriz, A. J., et al. (2015). In vivo genome editing using Staphylococcus aureus Cas9. Nature, 520(7546), 186–191.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rui, Y., Wilson, D. R., Sanders, K., & Green, J. J. (2019a). Reducible branched Ester-amine quadpolymers (rBEAQs) codelivering plasmid DNA and RNA oligonucleotides enable CRISPR/Cas9 genome editing. ACS Applied Materials & Interfaces, 11(11), 10472–10480.

    Article  CAS  Google Scholar 

  • Rui, Y., Wilson, D. R., Choi, J., Varanasi, M., Sanders, K., Karlsson, J., et al. (2019b). Carboxylated branched poly (β-amino ester) nanoparticles enable robust cytosolic protein delivery and CRISPR-Cas9 gene editing. Science Advances, 5(12), eaay3255.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rui, Y., Wilson, D. R., & Green, J. J. (2019c). Non-viral delivery to enable genome editing. Trends in Biotechnology, 37(3), 281–293.

    Article  CAS  PubMed  Google Scholar 

  • Rui, Y., Varanasi, M., Mendes, S., Yamagata, H. M., Wilson, D. R., & Green, J. J. (2020). Poly (Beta-Amino Ester) nanoparticles enable nonviral delivery of CRISPR-Cas9 plasmids for gene knockout and gene deletion. Molecular Therapy--Nucleic Acids, 20, 661–672.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ryu, N., Kim, M.-A., Park, D., Lee, B., Kim, Y.-R., Kim, K.-H., et al. (2018). Effective PEI-mediated delivery of CRISPR-Cas9 complex for targeted gene therapy. Nanomedicine: Nanotechnology, Biology and Medicine, 14(7), 2095–2102.

    Article  CAS  Google Scholar 

  • Schumann, K., Lin, S., Boyer, E., Simeonov, D. R., Subramaniam, M., Gate, R. E., et al. (2015). Generation of knock-in primary human T cells using Cas9 ribonucleoproteins. Proceedings of the National Academy of Sciences, 112(33), 10437–10442.

    Article  CAS  Google Scholar 

  • Shakeri, S., Ashrafizadeh, M., Zarrabi, A., Roghanian, R., Afshar, E. G., Pardakhty, A., et al. (2020). Multifunctional polymeric nanoplatforms for brain diseases diagnosis, therapy and theranostics. Biomedicine, 8(1), 13.

    CAS  Google Scholar 

  • Slaymaker, I. M., Gao, L., Zetsche, B., Scott, D. A., Yan, W. X., & Zhang, F. (2016). Rationally engineered Cas9 nucleases with improved specificity. Science, 351(6268), 84–88.

    Article  CAS  PubMed  Google Scholar 

  • Sun, W., Ji, W., Hall, J. M., Hu, Q., Wang, C., Beisel, C. L., et al. (2015). Self-assembled DNA nanoclews for the efficient delivery of CRISPR–Cas9 for genome editing. Angewandte Chemie, 127(41), 12197–12201.

    Article  Google Scholar 

  • Sun, W., Wang, J., Hu, Q., Zhou, X., Khademhosseini, A., & Gu, Z. (2020). CRISPR-Cas12a delivery by DNA-mediated bioresponsive editing for cholesterol regulation. Science Advances, 6(21), eaba2983.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sung, Y. K., & Kim, S. (2019). Recent advances in the development of gene delivery systems. Biomaterials Research, 23(1), 1–7.

    Article  Google Scholar 

  • Swiech, L., Heidenreich, M., Banerjee, A., Habib, N., Li, Y., Trombetta, J., et al. (2015). In vivo interrogation of gene function in the mammalian brain using CRISPR-Cas9. Nature Biotechnology, 33(1), 102–106.

    Article  CAS  PubMed  Google Scholar 

  • Taharabaru, T., Yokoyama, R., Higashi, T., Mohammed, A. F. A., Inoue, M., Maeda, Y., et al. (2020). Genome editing in a wide area of the brain using dendrimer-based ternary polyplexes of Cas9 ribonucleoprotein. ACS Applied Materials & Interfaces, 12(19), 21386–21397.

    Article  CAS  Google Scholar 

  • Tan, Z., Jiang, Y., Ganewatta, M. S., Kumar, R., Keith, A., Twaroski, K., et al. (2019). Block polymer micelles enable CRISPR/Cas9 ribonucleoprotein delivery: Physicochemical properties affect packaging mechanisms and gene editing efficiency. Macromolecules, 52(21), 8197–8206.

    Article  CAS  Google Scholar 

  • Travis, J. (2015). Germline editing dominates DNA summit. American Association for the Advancement of Science.

    Book  Google Scholar 

  • Wan, T., Chen, Y., Pan, Q., Xu, X., Kang, Y., Gao, X., et al. (2020). Genome editing of mutant KRAS through supramolecular polymer-mediated delivery of Cas9 ribonucleoprotein for colorectal cancer therapy. Journal of Controlled Release, 322, 236–247.

    Article  CAS  PubMed  Google Scholar 

  • Wang, M., Liu, H., Li, L., & Cheng, Y. (2014). A fluorinated dendrimer achieves excellent gene transfection efficacy at extremely low nitrogen to phosphorus ratios. Nature Communications, 5(1), 1–8.

    Google Scholar 

  • Wang, D., Mou, H., Li, S., Li, Y., Hough, S., Tran, K., et al. (2015). Adenovirus-mediated somatic genome editing of Pten by CRISPR/Cas9 in mouse liver in spite of Cas9-specific immune responses. Human Gene Therapy, 26(7), 432–442.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang, H., La Russa, M., & Qi, L. S. (2016). CRISPR/Cas9 in genome editing and beyond. Annual Review of Biochemistry, 85, 227–264.

    Article  CAS  PubMed  Google Scholar 

  • Wang, H.-X., Li, M., Lee, C. M., Chakraborty, S., Kim, H.-W., Bao, G., et al. (2017). CRISPR/Cas9-based genome editing for disease modeling and therapy: Challenges and opportunities for nonviral delivery. Chemical Reviews, 117(15), 9874–9906.

    Article  CAS  PubMed  Google Scholar 

  • Wang, Y., Ma, B., Abdeen, A. A., Chen, G., Xie, R., Saha, K., et al. (2018). Versatile redox-responsive polyplexes for the delivery of plasmid DNA, messenger RNA, and CRISPR-Cas9 genome-editing machinery. ACS Applied Materials & Interfaces, 10(38), 31915–31927.

    Article  CAS  Google Scholar 

  • Wu, S.-S., Li, Q.-C., Yin, C.-Q., Xue, W., & Song, C.-Q. (2020). Advances in CRISPR/Cas-based gene therapy in human genetic diseases. Theranostics, 10(10), 4374.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu, C., Lu, Z., Luo, Y., Liu, Y., Cao, Z., Shen, S., et al. (2018). Targeting of NLRP3 inflammasome with gene editing for the amelioration of inflammatory diseases. Nature Communications, 9(1), 1–14.

    Article  Google Scholar 

  • Xu, C.-F., Chen, G.-J., Luo, Y.-L., Zhang, Y., Zhao, G., Lu, Z.-D., et al. (2021). Rational designs of in vivo CRISPR-Cas delivery systems. Advanced Drug Delivery Reviews, 168, 3–29.

    Article  CAS  PubMed  Google Scholar 

  • Yan, M., Wen, J., Liang, M., Lu, Y., Kamata, M., & Chen, I. S. (2015). Modulation of gene expression by polymer nanocapsule delivery of DNA cassettes encoding small RNAs. PLoS One, 10(6), e0127986.

    Article  PubMed  PubMed Central  Google Scholar 

  • Yang, J., Zhang, Q., Chang, H., & Cheng, Y. (2015). Surface-engineered dendrimers in gene delivery. Chemical Reviews, 115(11), 5274–5300.

    Article  CAS  PubMed  Google Scholar 

  • Yin, H., Song, C.-Q., Dorkin, J. R., Zhu, L. J., Li, Y., Wu, Q., et al. (2016). Therapeutic genome editing by combined viral and non-viral delivery of CRISPR system components in vivo. Nature Biotechnology, 34(3), 328–333.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yue, H., Zhou, X., Cheng, M., & Xing, D. (2018). Graphene oxide-mediated Cas9/sgRNA delivery for efficient genome editing. Nanoscale, 10(3), 1063–1071.

    Article  CAS  PubMed  Google Scholar 

  • Zhang, Z., Wan, T., Chen, Y., Chen, Y., Sun, H., Cao, T., et al. (2019a). Cationic polymer-mediated CRISPR/Cas9 plasmid delivery for genome editing. Macromolecular Rapid Communications, 40(5), 1800068.

    Article  Google Scholar 

  • Zhang, Z., Wang, Q., Liu, Q., Zheng, Y., Zheng, C., Yi, K., et al. (2019b). Dual-locking nanoparticles disrupt the PD-1/PD-L1 pathway for efficient cancer immunotherapy. Advanced Materials, 31(51), 1905751.

    Article  CAS  Google Scholar 

  • Zhang, X., Xu, C., Gao, S., Li, P., Kong, Y., Li, T., et al. (2019c). CRISPR/Cas9 delivery mediated with hydroxyl-rich nanosystems for gene editing in aorta. Advanced Science, 6(12), 1900386.

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang, H.-X., Zhang, Y., & Yin, H. (2019d). Genome editing with mRNA encoding ZFN, TALEN, and Cas9. Molecular Therapy, 27(4), 735–746.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang, Y., Shen, S., Zhao, G., Xu, C.-F., Zhang, H.-B., Luo, Y.-L., et al. (2019e). In situ repurposing of dendritic cells with CRISPR/Cas9-based nanomedicine to induce transplant tolerance. Biomaterials, 217, 119302.

    Article  CAS  PubMed  Google Scholar 

  • Zhang, S., Shen, J., Li, D., & Cheng, Y. (2021). Strategies in the delivery of Cas9 ribonucleoprotein for CRISPR/Cas9 genome editing. Theranostics, 11(2), 614.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhu, D., Shen, H., Tan, S., Hu, Z., Wang, L., Yu, L., et al. (2018). Nanoparticles based on poly (β-Amino Ester) and HPV16-targeting CRISPR/shRNA as potential drugs for HPV16-related cervical malignancy. Molecular Therapy, 26(10), 2443–2455.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Declaration of Interests

The authors declare no competing interests.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Feik School of Pharmacy, University of the Incarnate Word, San Antonio, TX, USA

    Shoaib Iqbal

  2. Department of Bioengineering, Clemson University, Clemson, SC, USA

    Angela Alexander-Bryant & Jessica Larsen

  3. Department of Chemical and Biomolecular Engineering, Clemson University, Clemson, SC, USA

    Jessica Larsen

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  1. Shoaib Iqbal
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  2. Angela Alexander-Bryant
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  3. Jessica Larsen
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Correspondence to Jessica Larsen .

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Editors and Affiliations

  1. Department of Chemical Engineering, University of Washington, Seattle, WA, USA

    Elizabeth Nance

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Iqbal, S., Alexander-Bryant, A., Larsen, J. (2022). Polymer-Mediated Delivery of CRISPR-Cas9 Genome-Editing Therapeutics for CNS Disease. In: Nance, E. (eds) Engineering Biomaterials for Neural Applications. Springer, Cham. https://doi.org/10.1007/978-3-031-11409-0_6

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