Skip to content
2000
  1. Home
  2. A-Z Publications
  3. MicroRNA
  4. Fast Track Articles
  5. Fast Track Article
image of Nanoparticle Carriers: A New Era of Precise CRISPR/Cas9 Gene Editing

Abstract

The revolutionary CRISPR/Cas9 gene editing technology holds immense potential for treating genetic diseases and tackling conditions like cancer. However, efficient delivery remains a significant challenge. This is where nanoparticles come into play, emerging as powerful allies in the realm of drug delivery. Nanoparticles can accommodate larger insertion sizes, enabling the incorporation of larger Cas9 enzymes and complex guide RNAs, thus opening up the possibility of editing previously inaccessible genetic regions. Their relatively straightforward and scalable production processes make them cost-effective options for wider applications. Notably, nanoparticles excel , demonstrating efficient tissue penetration and targeted delivery, which are crucial for maximizing therapeutic impact while minimizing side effects.

This review aims to explore the potential of nanoparticle-based delivery systems for CRISPR/Cas9, highlighting their advantages and challenges in gene editing applications. The diverse range of nanoparticles further bolsters their potential. Polymeric nanoparticles, for instance, offer tunable properties for customization and controlled release of the CRISPR cargo. Lipid-based nanoparticles facilitate efficient cellular uptake and endosomal escape, ensuring the CRISPR components reach the target DNA. Even gold nanoparticles, known for their unique biocompatibility and photothermal properties, hold promise in light-activated editing strategies. Non-viral delivery systems, particularly those based on nanoparticles, stand out due to their inherent advantages.

Collectively, the evidence paints a promising picture: nanoparticles are not merely passive carriers but active participants in the CRISPR/Cas9 delivery landscape. Their versatility, efficiency, and safety position them as key enablers of a future where gene editing can revolutionize drug development, offering personalized and targeted therapies for a wide range of diseases.

© 2024 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/mirna/10.2174/0122115366319848241022092805
2024-10-31
2025-06-25

  • From This Site

    /content/journals/mirna/10.2174/0122115366319848241022092805
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Barrangou R. Horvath P. A decade of discovery: CRISPR functions and applications. Nat. Microbiol. 2017 2 7 17092 10.1038/nmicrobiol.2017.92 28581505
    [Google Scholar]
  2. Makarova K.S. Zhang F. Koonin E.V. SnapShot: Class 2 CRISPR-Cas systems. Cell 2017 168 (1-2) 328
    [Google Scholar]
  3. 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 6096 816 821 10.1126/science.1225829 22745249
    [Google Scholar]
  4. Zhang J. Rouillon C. Kerou M. Reeks J. Brugger K. Graham S. Reimann J. Cannone G. Liu H. Albers S.V. Naismith J.H. Spagnolo L. White M.F. Structure and mechanism of the CMR complex for CRISPR-mediated antiviral immunity. Mol. Cell 2012 45 3 303 313 10.1016/j.molcel.2011.12.013 22227115
    [Google Scholar]
  5. Hochstrasser M.L. Doudna J.A. Cutting it close: CRISPR-associated endoribonuclease structure and function. Trends Biochem. Sci. 2015 40 1 58 66 10.1016/j.tibs.2014.10.007 25468820
    [Google Scholar]
  6. Hsu P.D. Lander E.S. Zhang F. Development and applications of CRISPR-Cas9 for genome engineering. Cell 2014 157 6 1262 1278 10.1016/j.cell.2014.05.010 24906146
    [Google Scholar]
  7. Alkhnbashi O.S. Meier T. Mitrofanov A. Backofen R. Voß B. CRISPR-Cas bioinformatics. Methods 2020 172 3 11 10.1016/j.ymeth.2019.07.013 31326596
    [Google Scholar]
  8. Sapranauskas R. Gasiunas G. Fremaux C. Barrangou R. Horvath P. Siksnys V. The Streptococcus thermophilus CRISPR/Cas system provides immunity in Escherichia coli Nucleic Acids Res. 2011 39 21 9275 9282 10.1093/nar/gkr606 21813460
    [Google Scholar]
  9. Xu X. Wan T. Xin H. Li D. Pan H. Wu J. Ping Y. Delivery of CRISPR/Cas9 for therapeutic genome editing. J. Gene Med. 2019 21 7 e3107 10.1002/jgm.3107 31237055
    [Google Scholar]
  10. Tong S. Moyo B. Lee C.M. Leong K. Bao G. Engineered materials for in vivo delivery of genome-editing machinery. Nat. Rev. Mater. 2019 4 11 726 737 10.1038/s41578‑019‑0145‑9 34094589
    [Google Scholar]
  11. Parra-Nieto J. del Cid M.A.G. de Cárcer I.A. Baeza A. Inorganic porous nanoparticles for drug delivery in antitumoral therapy. Biotechnol. J. 2021 16 2 2000150 10.1002/biot.202000150 32476279
    [Google Scholar]
  12. Adams D. Gonzalez H. Deliliers J. Patisiran efficacy and safety for transthyretin amyloidosis polyneuropathy. N. Engl. J. Med. 2018 379 20 1953 1963 10.1056/NEJMoa1801091
    [Google Scholar]
  13. Akintayo A. Akintayo T. Adeyemo A.A. Lipid nanoparticles for cell and gene delivery: A promising approach for targeted delivery to solid tumors. Drug Deliv. Transl. Res. 2012 2 4 206 222 10.1007/s13346‑012‑0140‑6
    [Google Scholar]
  14. Lv H. Zhang W. Wang B. Surface charge density-dependent endocytosis and intracellular trafficking of cationic lipid nanoparticles. ACS Nano 2014 8 2 1250 1262 10.1021/nn405554m
    [Google Scholar]
  15. Ten Hoeve W. Heise A. Zuhorn-Klemm E. Design of polymeric nanocarriers for intracellular delivery. Chem. Rev. 2017 117 16 10746 11071 10.1021/acs.chemrev.600709b
    [Google Scholar]
  16. Gillet L. Bolaños P. Díez I. Stimuli-responsive nanocarriers for enhanced intracellular delivery of CRISPR/Cas9 ribonucleoprotein complexes. ACS Nano 2017 11 4 3334 3344 10.1021/acsnano.7b00701
    [Google Scholar]
  17. Zheng L. Bandara S.R. Tan Z. Leal C. Lipid nanoparticle topology regulates endosomal escape and delivery of RNA to the cytoplasm. Proc. Natl. Acad. Sci. USA 2023 120 27 e2301067120 10.1073/pnas.2301067120 37364130
    [Google Scholar]
  18. Jiang W. Bikard D. Cox D.B. CRISPR-Cas9 editing of DNA repair genes reveals an unexpected role of Mre11 in non-homologous recombination. DNA Repair (Amst.) 2015 35 70 76 10.1016/j.dnarep.2015.05.004
    [Google Scholar]
  19. Yang H. Wang H. Shivalila C.S. Cheng A.W. Shi L. Jaenisch R. One-step generation of mice carrying reporter and conditional alleles by CRISPR/Cas-mediated genome engineering. Cell 2013 154 6 1370 1379 10.1016/j.cell.2013.08.022 23992847
    [Google Scholar]
  20. Chew W.L. Tabebordbar M. Cheng J.K.W. Mali P. Wu E.Y. Ng A.H.M. Zhu K. Wagers A.J. Church G.M. A multifunctional AAV–CRISPR–Cas9 and its host response. Nat. Methods 2016 13 10 868 874 10.1038/nmeth.3993 27595405
    [Google Scholar]
  21. Paquet D. Kwart D. Chen A. Sproul A. Jacob S. Teo S. Olsen K.M. Gregg A. Noggle S. Tessier-Lavigne M. Efficient introduction of specific homozygous and heterozygous mutations using CRISPR/Cas9. Nature 2016 533 7601 125 129 10.1038/nature17664 27120160
    [Google Scholar]
  22. Carter B.J. Adeno-associated virus and the development of adeno-associated virus vectors: A historical perspective. Mol. Ther. 2004 10 6 981 989 10.1016/j.ymthe.2004.09.011 15564130
    [Google Scholar]
  23. Hastie E. Samulski R.J. Adeno-associated virus at 50: A golden anniversary of discovery, research, and gene therapy success - a personal perspective. Hum. Gene Ther. 2015 26 5 257 265 10.1089/hum.2015.025 25807962
    [Google Scholar]
  24. Kotterman M.A. Chalberg T.W. Schaffer D.V. Viral vectors for gene therapy: Translational and clinical outlook. Annu. Rev. Biomed. Eng. 2015 17 1 63 89 10.1146/annurev‑bioeng‑071813‑104938 26643018
    [Google Scholar]
  25. Lee C.S. Bishop E.S. Zhang R. Yu X. Farina E.M. Yan S. Zhao C. Zeng Z. Shu Y. Wu X. Lei J. Li Y. Zhang W. Yang C. Wu K. Wu Y. Ho S. Athiviraham A. Lee M.J. Wolf J.M. Reid R.R. He T.C. Adenovirus-mediated gene delivery: Potential applications for gene and cell-based therapies in the new era of personalized medicine. Genes Dis. 2017 4 2 43 63 10.1016/j.gendis.2017.04.001 28944281
    [Google Scholar]
  26. Song R. Murphy M. Li C. Ting K. Soo C. Zheng Z. Current development of biodegradable polymeric materials for biomedical applications. Drug Des. Devel. Ther. 2018 12 3117 3145 10.2147/DDDT.S165440 30288019
    [Google Scholar]
  27. Hanafy N. El-Kemary M. Leporatti S. Micelles structure development as a strategy to improve smart cancer therapy. Cancers 2018 10 7 238 10.3390/cancers10070238 30037052
    [Google Scholar]
  28. Gothwal A. Khan I. Gupta U. Polymeric micelles: Recent advancements in the delivery of anticancer drugs. Pharm. Res. 2016 33 1 18 39 10.1007/s11095‑015‑1784‑1 26381278
    [Google Scholar]
  29. Chai M.H. Unique structure and property of dendrimers in biomedical applications. Proceedings of the Royal Society A 2010 466 2117 1441 1443
    [Google Scholar]
  30. Sharma A.K. Prasher P. Aljabali A.A. Mishra V. Gandhi H. Kumar S. Mutalik S. Chellappan D.K. Tambuwala M.M. Dua K. Kapoor D.N. Emerging era of “somes”: Polymersomes as versatile drug delivery carrier for cancer diagnostics and therapy. Drug Deliv. Transl. Res. 2020 10 5 1171 1190 10.1007/s13346‑020‑00789‑2 32504410
    [Google Scholar]
  31. Wu D. Xu X. Exploring cutting-edge hydrogel technologies and their biomedical applications. Bioact. Mater. 2018 3 4 446 447 10.1016/j.bioactmat.2018.08.001 30182071
    [Google Scholar]
  32. Mohammadi-Samani S. Ghasemiyeh P. Solid lipid nanoparticles and nanostructured lipid carriers as novel drug delivery systems: Applications, advantages and disadvantages. Res. Pharm. Sci. 2018 13 4 288 303 10.4103/1735‑5362.235156 30065762
    [Google Scholar]
  33. Battaglia L. Gallarate M. Lipid nanoparticles: State of the art, new preparation methods and challenges in drug delivery. Expert Opin. Drug Deliv. 2012 9 5 497 508 10.1517/17425247.2012.673278 22439808
    [Google Scholar]
  34. Taratula O. Kuzmov A. Shah M. Garbuzenko O.B. Minko T. Nanostructured lipid carriers as multifunctional nanomedicine platform for pulmonary co-delivery of anticancer drugs and siRNA. J. Control. Release 2013 171 3 349 357 10.1016/j.jconrel.2013.04.018 23648833
    [Google Scholar]
  35. Yanar F. Mosayyebi A. Nastruzzi C. Carugo D. Zhang X. Continuous-flow production of liposomes with a millireactor under varying fluidic conditions. Pharmaceutics 2020 12 11 1001 10.3390/pharmaceutics12111001 33105650
    [Google Scholar]
  36. Felgner P.L. Gadek T.R. Holm M. Roman R. Chan H.W. Wenz M. Northrop J.P. Ringold G.M. Danielsen M. Lipofection: A highly efficient, lipid-mediated DNA-transfection procedure. Proc. Natl. Acad. Sci. USA 1987 84 21 7413 7417 10.1073/pnas.84.21.7413 2823261
    [Google Scholar]
  37. Abdelkader H. Alani A.W.G. Alany R.G. Recent advances in non-ionic surfactant vesicles (niosomes): Self-assembly, fabrication, characterization, drug delivery applications and limitations. Drug Deliv. 2014 21 2 87 100 10.3109/10717544.2013.838077 24156390
    [Google Scholar]
  38. Ag Seleci D. Maurer V. Stahl F. Scheper T. Garnweitner G. Rapid microfluidic preparation of niosomes for targeted drug delivery. Int. J. Mol. Sci. 2019 20 19 4696 10.3390/ijms20194696 31546717
    [Google Scholar]
  39. Aslan C. Zolbanin N.M. Faraji F. Jafari R. Exosomes for CRISPR-Cas9 delivery: the cutting edge in genome editing. Mol. Biotechnol. 2023 1 25 10.1007/s12033‑023‑00932‑7 38012525
    [Google Scholar]
  40. Duan L. Ouyang K. Xu X. Xu L. Wen C. Zhou X. Qin Z. Xu Z. Sun W. Liang Y. Nanoparticle delivery of CRISPR/Cas9 for genome editing. Front. Genet. 2021 12 673286 10.3389/fgene.2021.673286 34054927
    [Google Scholar]
  41. Lin-Shiao E. Pfeifer W.G. Shy B.R. Saffari Doost M. Chen E. Vykunta V.S. Hamilton J.R. Stahl E.C. Lopez D.M. Sandoval Espinoza C.R. Deyanov A.E. Lew R.J. Poirer M.G. Marson A. Castro C.E. Doudna J.A. CRISPR–Cas9-mediated nuclear transport and genomic integration of nanostructured genes in human primary cells. Nucleic Acids Res. 2022 50 3 1256 1268 10.1093/nar/gkac049 35104875
    [Google Scholar]
  42. Sun W. Jiang T. Lu Y. Reiff M. Mo R. Gu Z. Cocoon-like self-degradable DNA nanoclew for anticancer drug delivery. J. Am. Chem. Soc. 2014 136 42 14722 14725 10.1021/ja5088024 25336272
    [Google Scholar]
  43. Bahl E. Jyoti A. Singh A. Siddqui A. Upadhyay S.K. Jain D. Shah M.P. Saxena J. Nanomaterials for intelligent CRISPR-Cas tools: Improving environment sustainability. Environ. Sci. Pollut. Res. Int. 2024 1 7 10.1007/s11356‑024‑32101‑x 38291210
    [Google Scholar]
  44. García-Fernández A. Vivo-Llorca G. Sancho M. García-Jareño A. Ramírez-Jiménez L. Barber-Cano E. Murguía J. Orzáez M. Sancenón F. Martínez-Máñez R. Nanodevices for the efficient codelivery of CRISPR-Cas9 editing machinery and an entrapped cargo: A proposal for dual anti-inflammatory therapy. Pharmaceutics 2022 14 7 1495 10.3390/pharmaceutics14071495 35890389
    [Google Scholar]
  45. Li Y. Li C. Yan J. Liao Y. Qin C. Wang L. Huang Y. Yang C. Wang J. Ding X. Yang Y.Y. Yuan P. Polymeric micellar nanoparticles for effective CRISPR/Cas9 genome editing in cancer. Biomaterials 2024 309 122573 10.1016/j.biomaterials.2024.122573 38677222
    [Google Scholar]
  46. Zhang C. Wang X. Liu G. Ren H. Li J. Jiang Z. Liu J. Lovell J.F. Zhang Y. Metal coordination micelles for anti-cancer treatment by gene-editing and phototherapy. J. Control. Release 2023 357 210 221 10.1016/j.jconrel.2023.03.042 36972864
    [Google Scholar]
  47. Zhang C. Wang X. Liu G. Ren H. Liu J. Jiang Z. Zhang Y. CRISPR/Cas9 and chlorophyll coordination micelles for cancer treatment by genome editing and photodynamic therapy. Small 2023 19 17 2206981 10.1002/smll.202206981 36693779
    [Google Scholar]
  48. Tan Z. Jiang Y. Ganewatta M.S. Kumar R. Keith A. Twaroski K. Pengo T. Tolar J. Lodge T.P. Reineke T.M. Block polymer micelles enable CRISPR/Cas9 ribonucleoprotein delivery: Physicochemical properties affect packaging mechanisms and gene editing efficiency. Macromolecules 2019 52 21 8197 8206 10.1021/acs.macromol.9b01645
    [Google Scholar]
  49. Zamolo S.J. Darbre T. Reymond J.L. Transfecting tissue models with CRISPR/Cas9 plasmid DNA using peptide dendrimers. Chem. Commun. 2020 56 80 11981 11984 10.1039/D0CC04750C 32895670
    [Google Scholar]
  50. Liu C. Wan T. Wang H. Zhang S. Ping Y. Cheng Y. A boronic acid–rich dendrimer with robust and unprecedented efficiency for cytosolic protein delivery and CRISPR-Cas9 gene editing. Sci. Adv. 2019 5 6 eaaw8922 10.1126/sciadv.aaw8922 31206027
    [Google Scholar]
  51. Pérez-Sosa C. Pérez M.S. Vallejo-Janeta A.P. Bhansali S. Miriuka S. Lerner B. Droplets for gene editing using CRISPR-Cas9 and clonal selection improvement using hydrogels. Micromachines 2024 15 3 413 10.3390/mi15030413 38542660
    [Google Scholar]
  52. Eswaran L. Kazimirsky G. Byk G. New biocompatible nanohydrogels of predefined sizes for complexing nucleic acids. Pharmaceutics 2023 15 2 332 10.3390/pharmaceutics15020332 36839655
    [Google Scholar]
  53. Roh Y.H. Lee C.Y. Lee S. Kim H. Ly A. Castro C.M. Cheon J. Lee J.H. Lee H. CRISPR‐enhanced hydrogel microparticles for multiplexed detection of nucleic acids. Adv. Sci. 2023 10 10 2206872 10.1002/advs.202206872 36725305
    [Google Scholar]
  54. Zhao R. Tang Y. Song D. Liu M. Li B. CRISPR/Cas12a-responsive hydrogels for conjugation-free and universal indicator release in colorimetric detection. Anal. Chem. 2023 95 50 18522 18529 10.1021/acs.analchem.3c03900 38055961
    [Google Scholar]
  55. Zhang T. Applications of lipid nanoparticles in CRISPR technology. MedScien 2024 1 7 10.61173/ecc6db10
    [Google Scholar]
  56. Palanki R. Han E.L. Murray A.M. Maganti R. Tang S. Swingle K.L. Kim D. Yamagata H. Safford H.C. Mrksich K. Peranteau W.H. Mitchell M.J. Optimized microfluidic formulation and organic excipients for improved lipid nanoparticle mediated genome editing. Lab Chip 2024 24 16 3790 3801 10.1039/D4LC00283K 39037068
    [Google Scholar]
  57. Yang S. Im S.H. Chung J.Y. Lee J. Lee K.H. Kang Y.K. Chung H.J. An Antibody‐CRISPR/Cas conjugate platform for target‐specific delivery and gene editing in cancer. Adv. Sci. (Weinh.) 2024 11 21 2308763 10.1002/advs.202308763
    [Google Scholar]
  58. Walther J. Porenta D. Wilbie D. Seinen C. Benne N. Yang Q. de Jong O.G. Lei Z. Mastrobattista E. Comparative analysis of lipid nanoparticle-mediated delivery of CRISPR-Cas9 RNP versus mRNA/sgRNA for gene editing in vitro and in vivo Eur. J. Pharm. Biopharm. 2024 196 114207 10.1016/j.ejpb.2024.114207 38325664
    [Google Scholar]
  59. Sun Q. Zhang H. Ding F. Gao X. Zhu Z. Yang C. Development of ionizable lipid nanoparticles and a lyophilized formulation for potent CRISPR-Cas9 delivery and genome editing. Int. J. Pharm. 2024 652 123845 10.1016/j.ijpharm.2024.123845 38266942
    [Google Scholar]
  60. Geczy R. Thommandru B. Swaminathan M. Zhao R. Tan K. Low K. Balgi A. Park S. Watt E. Thada V. Rettig G. Zhang A. Turk R. Clarke S. Lipid nanoparticle-mediated gene editing of human primary T cells and off-target analysis of the CRISPR-Cas9 indels. Blood 2023 142 Suppl. 1 6833 10.1182/blood‑2023‑185068
    [Google Scholar]
  61. Chen K. Han H. Zhao S. Xu B. Yin B. Trinidad M. Burgstone B.W. Murthy N. Doudna J.A. Lung and liver editing by lipid nanoparticle delivery of a stable CRISPR-Cas9 RNP. bioRxiv 2023 2023 566339 10.1101/2023.11.15.566339
    [Google Scholar]
  62. Alhazza A. Mahdipoor P. Hall R. Manda A. Lohan S. Parang K. Aliabadi H.M. Modifying peptide/lipid-associated nucleic acids (PLANAs) for CRISPR/Cas9 ribonucleoprotein delivery. Eur. J. Pharm. Sci. 2024 195 106708 10.1016/j.ejps.2024.106708 38262570
    [Google Scholar]
  63. Ju H Kim D Oh YK Lipid nanoparticle-mediated CRISPR/Cas9 gene editing and metabolic engineering for anticancer immunotherapy. Asian J Pharm Sci. 2022 17 5 641 652
    [Google Scholar]
  64. Fu J.Y. Preparation method of CRISPR/Cas9 targeted delivery system based on albumin. C.N. Patent 115844831B 2022
  65. Amy C.H. Delivering CRISPR therapeutics with lipid nanoparticles. U.S. Patent 10626393B2 2016
  66. Kallanthottathil G. Lipid formulations for gene editing. U.S. Patent 12024484B2 2021
  67. Zhang F. Delivery and use of the CRISPR-CAS systems, vectors and compositions for hepatic targeting and therapy. U.S. Patent 12018275B2 2023
/content/journals/mirna/10.2174/0122115366319848241022092805
Loading
Nanoparticle Carriers: A New Era of Precise CRISPR/Cas9 Gene Editing
Bentham Science Publishers ; https://doi.org/10.2174/0122115366319848241022092805
/content/journals/mirna/10.2174/0122115366319848241022092805
/content/journals/mirna/10.2174/0122115366319848241022092805
Loading

Data & Media loading...


  • Article Type:     Review Article
Keywords: CRISPR delivery process ; nanoparticles ; future aspects
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test