Skip to main content
SpringerLink
Log in

Multifunctional nucleic acid nanostructures for gene therapies

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

Abstract

Nucleic acid nanotechnology has been developed to be a promising strategy to construct various nano-biomaterials with structural programmability, spatial addressability, and excellent biocompatibility. Self-assembled nucleic acid nanostructures have been employed in a variety of biomedical applications, such as bio-imaging, diagnosis, and therapeutics. In this manuscript, we will review recent progress in the development of multifunctional nucleic acid nanostructures as gene drug delivery vehicles. Therapeutic systems based on RNA interference (RNAi), clustered regularly interspaced short palindromic repeat associated proteins 9 system (CRISPR/Cas9) genome editing, gene expression, and CpG-based immunostimulation will be highlighted. We will also discuss the challenges and future directions of nucleic acid nanotechnology in biomedical research.

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. Naldini, L. Gene therapy returns to centre stage. Nature 2015, 526, 351–360.

    Google Scholar 

  2. Kotterman, M. A.; Schaffer, D. V. Engineering adenoassociated viruses for clinical gene therapy. Nat. Rev. Genet. 2014, 15, 445–451.

    Google Scholar 

  3. Torchilin, V. P. Recent advances with liposomes as pharmaceutical carriers. Nat. Rev. Drug Discov. 2005, 4, 145–160.

    Google Scholar 

  4. Lächelt, U.; Wagner, E. Nucleic acid therapeutics using polyplexes: A journey of 50 years (and beyond). Chem. Rev. 2015, 115, 11043–11078.

    Google Scholar 

  5. Dufès, C.; Uchegbu, I. F.; Schätzlein, A. G. Dendrimers in gene delivery. Adv. Drug Deliv. Rev. 2005, 57, 2177–2202.

    Google Scholar 

  6. Sokolova, V.; Epple, M. Inorganic nanoparticles as carriers of nucleic acids into cells. Angew. Chem., Int. Ed. 2008, 47, 1382–1395.

    Google Scholar 

  7. Kallenbach, N. R.; Ma, R. I.; Seeman, N. C. An immobile nucleic acid junction constructed from oligonucleotides. Nature 1983, 305, 829–831.

    Google Scholar 

  8. Seeman, N. C. DNA in a material world. Nature 2003, 421, 427–431.

    Google Scholar 

  9. Zheng, J. P.; Birktoft, J. J.; Chen, Y.; Wang, T.; Sha, R. J.; Constantinou, P. E.; Ginell, S. L.; Mao, C. D.; Seeman, N. C. From molecular to macroscopic via the rational design of a self–assembled 3D DNA crystal. Nature 2009, 461, 74–77.

    Google Scholar 

  10. Seeman, N. C. Nanomaterials based on DNA. Annu. Rev. Biochem. 2010, 79, 65–87.

    Google Scholar 

  11. Winfree, E.; Liu, F. R.; Wenzler, L. A.; Seeman, N. C. Design and self–assembly of two–dimensional DNA crystals. Nature 1998, 394, 539–544.

    Google Scholar 

  12. Li, Y. G.; Tseng, Y. D.; Kwon, S. Y.; D'Espaux, L.; Bunch, J. S.; McEuen, P. L.; Luo, D. Controlled assembly of dendrimer–like DNA. Nat. Mater. 2004, 3, 38–42.

    Google Scholar 

  13. Goodman, R. P.; Berry, R. M.; Turberfield, A. J. The single–step synthesis of a DNA tetrahedron. Chem. Commun. 2004, 1372–1373.

    Google Scholar 

  14. Rothemund, P. W. K. Folding DNA to create nanoscale shapes and patterns. Nature 2006, 440, 297–302.

    Google Scholar 

  15. Ali, M. M.; Li, F.; Zhang, Z. Q.; Zhang, K. X.; Kang, D. K.; Ankrum, J. A.; Le, X. C.; Zhao, W. A. Rolling circle amplification: A versatile tool for chemical biology, materials science and medicine. Chem. Soc. Rev. 2014, 43, 3324–3341.

    Google Scholar 

  16. Scheffler, M.; Dorenbeck, A.; Jordan, S.; Wüstefeld, M.; von Kiedrowski, G. Self–assembly of trisoligonucleotidyls: The case for nano–acetylene and nano–cyclobutadiene. Angew. Chem., Int. Ed. 1999, 38, 3311–3315.

    Google Scholar 

  17. Lee, J. B.; Roh, Y. H.; Um, S. H.; Funabashi, H.; Cheng, W. L.; Cha, J. J.; Kiatwuthinon, P.; Muller, D. A.; Luo, D. Multifunctional nanoarchitectures from DNA–based ABC monomers. Nat. Nanotechnol. 2009, 4, 430–436.

    Google Scholar 

  18. Goodman, R. P.; Schaap, I. A. T.; Tardin, C. F.; Erben, C. M.; Berry, R. M.; Schmidt, C. F.; Turberfield, A. J. Rapid chiral assembly of rigid DNA building blocks for molecular nanofabrication. Science 2005, 310, 1661–1665.

    Google Scholar 

  19. Goodman, R. P.; Heilemann, M.; Doose, S.; Erben, C. M.; Kapanidis, A. N.; Turberfield, A. J. Reconfigurable, braced, three–dimensional DNA nanostructures. Nat. Nanotechnol. 2008, 3, 93–96.

    Google Scholar 

  20. Kato, T.; Goodman, R. P.; Erben, C. M.; Turberfield, A. J.; Namba, K. High–resolution structural analysis of a DNA nanostructure by cryoEM. Nano Lett. 2009, 9, 2747–2750.

    Google Scholar 

  21. Chen, J.; Seeman, N. C. Synthesis from DNA of a molecule with the connectivity of a cube. Nature 1991, 350, 631–633.

    Google Scholar 

  22. Erben, C. M.; Goodman, R. P.; Turberfield, A. J. A selfassembled DNA bipyramid. J. Am. Chem. Soc. 2007, 129, 6992–6993.

    Google Scholar 

  23. He, Y.; Su, M.; Fang, P. A.; Zhang, C.; Ribbe, A. E.; Jiang, W.; Mao, C. D. On the chirality of self–assembled DNA octahedra. Angew. Chem., Int. Ed. 2010, 49, 748–751.

    Google Scholar 

  24. He, Y.; Ye, T.; Su, M.; Zhang, C.; Ribbe, A. E.; Jiang, W.; Mao, C. D. Hierarchical self–assembly of DNA into symmetric supramolecular polyhedra. Nature 2008, 452, 198–201.

    Google Scholar 

  25. Saccà, B.; Meyer, R.; Erkelenz, M.; Kiko, K.; Arndt, A.; Schroeder, H.; Rabe, K. S.; Niemeyer, C. M. Orthogonal protein decoration of DNA origami. Angew. Chem., Int. Ed. 2010, 49, 9378–9383.

    Google Scholar 

  26. Tikhomirov, G.; Petersen, P.; Qian, L. L. Fractal assembly of micrometre–scale DNA origami arrays with arbitrary patterns. Nature 2017, 552, 67–71.

    Google Scholar 

  27. Lee, J. B.; Peng, S. M.; Yang, D. Y.; Roh, Y. H.; Funabashi, H.; Park, N.; Rice, E. J.; Chen, L. W.; Long, R.; Wu, M. M. et al. A mechanical metamaterial made from a DNA hydrogel. Nat. Nanotechnol. 2012, 7, 816–820.

    Google Scholar 

  28. Zhu, G. Z.; Hu, R.; Zhao, Z. L.; Chen, Z.; Zhang, X. B.; Tan, W. H. Noncanonical self–assembly of multifunctional DNA nanoflowers for biomedical applications. J. Am. Chem. Soc. 2013, 135, 16438–16445.

    Google Scholar 

  29. Hu, R.; Zhang, X. B.; Zhao, Z. L.; Zhu, G. Z.; Chen, T.; Fu, T.; Tan, W. H. DNA nanoflowers for multiplexed cellular imaging and traceable targeted drug delivery. Angew. Chem., Int. Ed. 2014, 53, 5821–5826.

    Google Scholar 

  30. Beyer, S.; Nickels, P.; Simmel, F. C. Periodic DNA nanotemplates synthesized by rolling circle amplification. Nano Lett. 2005, 5, 719–722.

    Google Scholar 

  31. Shchepinov, M. S.; Mir, K. U.; Elder, J. K.; Frank–Kamenetskii, M. D.; Southern, E. M. Oligonucleotide dendrimers: Stable nano–structures. Nucleic Acids Res. 1999, 27, 3035–3041.

    Google Scholar 

  32. Gothelf, K. V.; Thomsen, A.; Nielsen, M.; Cló, E.; Brown, R. S. Modular DNA–programmed assembly of linear and branched conjugated nanostructures. J. Am. Chem. Soc. 2004, 126, 1044–1046.

    Google Scholar 

  33. Aldaye, F. A.; Sleiman, H. F. Guest–mediated access to a single DNA nanostructure from a library of multiple assemblies. J. Am. Chem. Soc. 2007, 129, 10070–10071.

    Google Scholar 

  34. Stepp, B. R.; Gibbs–Davis, J. M.; Koh, D. L. F.; Nguyen, S. T. Cooperative melting in caged dimers of rigid small molecule–DNA hybrids. J. Am. Chem. Soc. 2008, 130, 9628–9629.

    Google Scholar 

  35. Zimmermann, J.; Cebulla, M. P. J.; Mönninghoff, S.; von Kiedrowski, G. Self–assembly of a DNA dodecahedron from 20 trisoligonucleotides with C3h linkers. Angew. Chem., Int. Ed. 2008, 47, 3626–3630.

    Google Scholar 

  36. Lo, P. K.; Karam, P.; Aldaye, F. A.; McLaughlin, C. K.; Hamblin, G. D.; Cosa, G.; Sleiman, H. F. Loading and selective release of cargo in DNA nanotubes with longitudinal variation. Nat. Chem. 2010, 2, 319–328.

    Google Scholar 

  37. Bhatia, D.; Mehtab, S.; Krishnan, R.; Indi, S. S.; Basu, A.; Krishnan, Y. Icosahedral DNA nanocapsules by modular assembly. Angew. Chem., Int. Ed. 2009, 48, 4134–4137.

    Google Scholar 

  38. Zhao, Z.; Jacovetty, E. L.; Liu, Y.; Yan, H. Encapsulation of gold nanoparticles in a DNA origami cage. Angew. Chem., Int. Ed. 2011, 50, 2041–2044.

    Google Scholar 

  39. Shen, X. B.; Song, C.; Wang, J. Y.; Shi, D. W.; Wang, Z. G.; Liu, N.; Ding, B. Q. Rolling up gold nanoparticle–dressed DNA origami into three–dimensional plasmonic chiral nanostructures. J. Am. Chem. Soc. 2012, 134, 146–149.

    Google Scholar 

  40. Shen, X. B.; Asenjo–Garcia, A.; Liu, Q.; Jiang, Q.; García de Abajo, F. J.; Liu, N.; Ding, B. Q. Three–dimensional plasmonic chiral tetramers assembled by DNA origami. Nano Lett. 2013, 13, 2128–2133.

    Google Scholar 

  41. Zhang, Y.; Chao, J.; Liu, H. J.; Wang, F.; Su, S.; Liu, B.; Zhang, L.; Shi, J. Y.; Wang, L. H.; Huang, W. et al. Transfer of two–dimensional oligonucleotide patterns onto stereocontrolled plasmonic nanostructures through DNAorigami–based nanoimprinting lithography. Angew. Chem., Int. Ed. 2016, 55, 8036–8040.

    Google Scholar 

  42. Modi, S.; Swetha, M. G.; Goswami, D.; Gupta, G. D.; Mayor, S.; Krishnan, Y. A DNA nanomachine that maps spatial and temporal pH changes inside living cells. Nat. Nanotechnol. 2009, 4, 325–330.

    Google Scholar 

  43. Modi, S.; Nizak, C.; Surana, S.; Halder, S.; Krishnan, Y. Two DNA nanomachines map pH changes along intersecting endocytic pathways inside the same cell. Nat. Nanotechnol. 2013, 8, 459–467.

    Google Scholar 

  44. Lu, Z. S.; Wang, Y.; Xu, D.; Pang, L. Aptamer–tagged DNA origami for spatially addressable detection of aflatoxin B1. Chem. Commun. 2017, 53, 941–944.

    Google Scholar 

  45. Bhatia, D.; Surana, S.; Chakraborty, S.; Koushika, S. P.; Krishnan, Y. A synthetic icosahedral DNA–based host–cargo complex for functional in vivo imaging. Nat. Commun. 2011, 2, 339.

    Google Scholar 

  46. Shen, X. B.; Jiang, Q.; Wang, J. Y.; Dai, L. R.; Zou, G. Z.; Wang, Z.–G.; Chen, W.–Q.; Jiang, W.; Ding, B. Q. Visualization of the intracellular location and stability of DNA origami with a label–free fluorescent probe. Chem. Commun. 2012, 48, 11301–11303.

    Google Scholar 

  47. Jiang, D. W.; Sun, Y. H.; Li, J.; Li, Q.; Lv, M.; Zhu, B.; Tian, T.; Cheng, D. F.; Xia, J. Y.; Zhang, L. et al. Multiplearmed tetrahedral DNA nanostructures for tumor–targeting, dual–modality in vivo imaging. ACS Appl. Mater. Interfaces 2016, 8, 4378–4384.

    Google Scholar 

  48. Chen, Y.–J.; Groves, B.; Muscat, R. A.; Seelig, G. DNA nanotechnology from the test tube to the cell. Nat. Nanotechnol. 2015, 10, 748–760.

    Google Scholar 

  49. Jiang, Q.; Song, C.; Nangreave, J.; Liu, X. W.; Lin, L.; Qiu, D. L.; Wang, Z.–G.; Zou, G. Z.; Liang, X. J.; Yan, H. et al. DNA origami as a carrier for circumvention of drug resistance. J. Am. Chem. Soc. 2012, 134, 13396–13403.

    Google Scholar 

  50. Zhao, Y. X.; Shaw, A.; Zeng, X. H.; Benson, E.; Nyström, A. M.; Högberg, B. DNA origami delivery system for cancer therapy with tunable release properties. ACS Nano 2012, 6, 8684–8691.

    Google Scholar 

  51. Liu, J.; Wei, T.; Zhao, J.; Huang, Y. Y.; Deng, H.; Kumar, A.; Wang, C. X.; Liang, Z. C.; Ma, X. W.; Liang, X.–J. Multifunctional aptamer–based nanoparticles for targeted drug delivery to circumvent cancer resistance. Biomaterials 2016, 91, 44–56.

    Google Scholar 

  52. Zhang, Q.; Jiang, Q.; Li, N.; Dai, L. R.; Liu, Q.; Song, L. L.; Wang, J. Y.; Li, Y. Q.; Tian, J.; Ding, B. Q. et al. DNA origami as an in vivo drug delivery vehicle for cancer therapy. ACS Nano 2014, 8, 6633–6643.

    Google Scholar 

  53. Du, Y.; Jiang, Q.; Beziere, N.; Song, L. L.; Zhang, Q.; Peng, D.; Chi, C. W.; Yang, X.; Guo, H. B.; Diot, G. et al. DNA–nanostructure–gold–nanorod hybrids for enhanced in vivo optoacoustic imaging and photothermal therapy. Adv. Mater. 2016, 28, 10000–10007.

    Google Scholar 

  54. Zhuang, X. X.; Ma, X. W.; Xue, X. D.; Jiang, Q.; Song, L. L.; Dai, L. R.; Zhang, C. Q.; Jin, S. B.; Yang, K.; Ding, B. Q. et al. A photosensitizer–loaded DNA origami nanosystem for photodynamic therapy. ACS Nano 2016, 10, 3486–3495.

    Google Scholar 

  55. Douglas, S. M.; Bachelet, I.; Church, G. M. A logic–gated nanorobot for targeted transport of molecular payloads. Science 2012, 335, 831–834.

    Google Scholar 

  56. Li, S. P.; Jiang, Q.; Liu, S. L.; Zhang, Y. L.; Tian, Y. H.; Song, C.; Wang, J.; Zou, Y. G.; Anderson, G. J.; Han, J. Y. et al. A DNA nanorobot functions as a cancer therapeutic in response to a molecular trigger in vivo. Nat. Biotechnol. 2018, 36, 258–264.

    Google Scholar 

  57. Li, J.; Zheng, C.; Cansiz, S.; Wu, C. C.; Xu, J. H.; Cui, C.; Liu, Y.; Hou, W. J.; Wang, Y. Y.; Zhang, L. Q. et al. Selfassembly of DNA nanohydrogels with controllable size and stimuli–responsive property for targeted gene regulation therapy. J. Am. Chem. Soc. 2015, 137, 1412–1415.

    Google Scholar 

  58. Park, N.; Um, S. H.; Funabashi, H.; Xu, J. F.; Luo, D. A cell–free protein–producing gel. Nat. Mater. 2009, 8, 432–437.

    Google Scholar 

  59. Hartman, M. R.; Yang, D. Y.; Tran, T. N. N.; Lee, K.; Kahn, J. S.; Kiatwuthinon, P.; Yancey, K. G.; Trotsenko, O.; Minko, S.; Luo, D. Thermostable branched DNA nanostructures as modular primers for polymerase chain reaction. Angew. Chem., Int. Ed. 2013, 52, 8699–8702.

    Google Scholar 

  60. Mohri, K.; Nishikawa, M.; Takahashi, N.; Shiomi, T.; Matsuoka, N.; Ogawa, K.; Endo, M.; Hidaka, K.; Sugiyama, H.; Takahashi, Y. et al. Design and development of nanosized DNA assemblies in polypod–like structures as efficient vehicles for immunostimulatory CpG motifs to immune cells. ACS Nano 2012, 6, 5931–5940.

    Google Scholar 

  61. Nishikawa, M.; Mizuno, Y.; Mohri, K.; Matsuoka, N.; Rattanakiat, S.; Takahashi, Y.; Funabashi, H.; Luo, D.; Takakura, Y. Biodegradable CpG DNA hydrogels for sustained delivery of doxorubicin and immunostimulatory signals in tumor–bearing mice. Biomaterials 2011, 32, 488–494.

    Google Scholar 

  62. Hong, C. A.; Eltoukhy, A. A.; Lee, H.; Langer, R.; Anderson, D. G.; Nam, Y. S. Dendrimeric siRNA for efficient gene silencing. Angew. Chem., Int. Ed. 2015, 54, 6740–6744.

    Google Scholar 

  63. Qu, Y. J.; Yang, J. J.; Zhan, P. F.; Liu, S. L.; Zhang, K.; Jiang, Q.; Li, C.; Ding, B. Q. Self–assembled DNA dendrimer nanoparticle for efficient delivery of immunostimulatory CpG motifs. ACS Appl. Mater. Interfaces 2017, 9, 20324–20329.

    Google Scholar 

  64. Lee, H.; Lytton–Jean, A. K.; Chen, Y.; Love, K. T.; Park, A. I.; Karagiannis, E. D.; Sehgal, A.; Querbes, W.; Zurenko, C. S.; Jayaraman, M. et al. Molecularly self–assembled nucleic acid nanoparticles for targeted in vivo siRNA delivery. Nat. Nanotechnol. 2012, 7, 389–393.

    Google Scholar 

  65. Ren, K. W.; Liu, Y.; Wu, J.; Zhang, Y.; Zhu, J.; Yang, M.; Ju, H. X. A DNA dual lock–and–key strategy for cell–subtypespecific siRNA delivery. Nat. Commun. 2016, 7, 13580.

    Google Scholar 

  66. Bujold, K. E.; Hsu, J. C. C.; Sleiman, H. F. Optimized DNA “nanosuitcases” for encapsulation and conditional release of siRNA. J. Am. Chem. Soc. 2016, 138, 14030–14038.

    Google Scholar 

  67. Fakhoury, J. J.; McLaughlin, C. K.; Edwardson, T. W.; Conway, J. W.; Sleiman, H. F. Development and characterization of gene silencing DNA cages. Biomacromolecules 2014, 15, 276–282.

    Google Scholar 

  68. Li, J.; Pei, H.; Zhu, B.; Liang, L.; Wei, M.; He, Y.; Chen, N.; Li, D.; Huang, Q.; Fan, C. H. Self–assembled multivalent DNA nanostructures for noninvasive intracellular delivery of immunostimulatory CpG oligonucleotides. ACS Nano 2011, 5, 8783–8789.

    Google Scholar 

  69. Schüller, V. J.; Heidegger, S.; Sandholzer, N.; Nickels, P. C.; Suhartha, N. A.; Endres, S.; Bourquin, C.; Liedl, T. Cellular immunostimulation by CpG–sequence–coated DNA origami structures. ACS Nano 2011, 5, 9696–9702.

    Google Scholar 

  70. Han, S.; Kim, H.; Lee, J. B. Library siRNA–generating RNA nanosponges for gene silencing by complementary rolling circle transcription. Sci. Rep. 2017, 7, 10005.

    Google Scholar 

  71. Lee, J. B.; Hong, J.; Bonner, D. K.; Poon, Z.; Hammond, P. T. Self–assembled RNA interference microsponges for efficient siRNA delivery. Nat. Mater. 2012, 11, 316–322.

    Google Scholar 

  72. Jang, M.; Kim, J. H.; Nam, H. Y.; Kwon, I. C.; Ahn, H. J. Design of a platform technology for systemic delivery of siRNA to tumours using rolling circle transcription. Nat. Commun. 2015, 6, 7930.

    Google Scholar 

  73. Ha, J. S.; Lee, J. S.; Jeong, J.; Kim, H.; Byun, J.; Sang, A. K.; Lee, H. J.; Chung, H. S.; Lee, J. B.; Ahn, D. R. PolysgRNA/siRNA ribonucleoprotein nanoparticles for targeted gene disruption. J. Control. Release 2017, 250, 27–35.

    Google Scholar 

  74. 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, 127, 12197–12201.

    Google Scholar 

  75. Ouyang, X. Y.; Li, J.; Liu, H. J.; Zhao, B.; Yan, J.; Ma, Y. Z.; Xiao, S. J.; Song, S. P.; Huang, Q.; Chao, J. et al. Rolling circle amplification–based DNA origami nanostructrures for intracellular delivery of immunostimulatory drugs. Small 2013, 9, 3082–3087.

    Google Scholar 

  76. Hong, C. A.; Lee, S. H.; Kim, J. S.; Park, J. W.; Bae, K. H.; Mok, H.; Park, T. G.; Lee, H. Gene silencing by siRNA microhydrogels via polymeric nanoscale condensation. J. Am. Chem. Soc. 2011, 133, 13914–13917.

    Google Scholar 

  77. Liu, J. B.; Wang, R. Y.; Ma, D. J.; Ouyang, D.; Xi, Z. Efficient construction of stable gene nanoparticles through polymerase chain reaction with flexible branched primers for gene delivery. Chem. Commun. 2015, 51, 9208–9211.

    Google Scholar 

  78. Ponnuswamy, N.; Bastings, M. M. C.; Nathwani, B.; Ryu, J. H.; Chou, L. Y. T.; Vinther, M.; Li, W. A.; Anastassacos, F. M.; Mooney, D. J.; Shih, W. M. Oligolysine–based coating protects DNA nanostructures from low–salt denaturation and nuclease degradation. Nat. Commun. 2017, 8, 15654.

    Google Scholar 

  79. Agarwal, N. P.; Matthies, M.; Gür, F. N.; Osada, K.; Schmidt, T. L. Block copolymer micellization as a protection strategy for DNA origami. Angew. Chem., Int. Ed. 2017, 56, 5460–5464.

    Google Scholar 

  80. Stephenson, M. L.; Zamecnik, P. C. Inhibition of Rous sarcoma viral RNA translation by a specific oligodeoxyribonucleotide. Proc. Natl. Acad. Sci. USA 1978, 75, 285–288.

    Google Scholar 

  81. Monia, B. P.; Johnston, J. F.; Geiger, T.; Muller, M.; Fabbro, D. Antitumor activity of a phosphorothioate antisense oligodeoxynucleotide targeted against C–raf kinase. Nat. Med. 1996, 2, 668–675.

    Google Scholar 

  82. Fire, A.; Xu, S. Q.; Montgomery, M. K.; Kostas, S. A.; Driver, S. E.; Mello, C. C. Potent and specific genetic interference by double–stranded RNA in Caenorhabditis elegans. Nature 1998, 391, 806–811.

    Google Scholar 

  83. Zamore, P. D.; Tuschl, T.; Sharp, P. A.; Bartel, D. P. RNAi: Double–stranded RNA directs the ATP–dependent cleavage of mRNA at 21 to 23 nucleotide intervals. Cell 2000, 101, 25–33.

    Google Scholar 

  84. Elbashir, S. M.; Harborth, J.; Lendeckel, W.; Yalcin, A.; Weber, K.; Tuschl, T. Duplexes of 21–nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 2001, 411, 494–498.

    Google Scholar 

  85. Brummelkamp, T. R.; Bernards, R.; Agami, R. A system for stable expression of short interfering RNAs in mammalian cells. Science 2002, 296, 550–553.

    Google Scholar 

  86. Lee, S. H.; Chung, B. H.; Park, T. G.; Nam, Y. S.; Mok, H. Small–interfering RNA (siRNA)–based functional microand nanostructures for efficient and selective gene silencing. Acc. Chem. Res. 2012, 45, 1014–1025.

    Google Scholar 

  87. Kanasty, R.; Dorkin, J. R.; Vegas, A.; Anderson, D. Delivery materials for siRNA therapeutics. Nat. Mater. 2013, 12, 967–977.

    Google Scholar 

  88. 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.

    Google Scholar 

  89. 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. A. et al. Multiplex genome engineering using CRISPR/Cas systems. Science 2013, 339, 819–823.

    Google Scholar 

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

    Google Scholar 

  91. Mali, P.; Yang, L. H.; Esvelt, K. M.; Aach, J.; Guell, M.; DiCarlo, J. E.; Norville, J. E.; Church, G. M. RNA–guided human genome engineering via Cas9. Science 2013, 339, 823–826.

    Google Scholar 

  92. Wang, H. Y.; Yang, H.; Shivalila, C. S.; Dawlaty, M. M.; Cheng, A. W.; Zhang, F.; Jaenisch, R. One–step generation of mice carrying mutations in multiple genes by CRISPR/Cas–mediated genome engineering. Cell 2013, 153, 910–918.

    Google Scholar 

  93. 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, 156, 836–843.

    Google Scholar 

  94. Hsu, P. D.; Lander, E. S.; Zhang, F. Development and applications of CRISPR–Cas9 for genome engineering. Cell 2014, 157, 1262–1278.

    Google Scholar 

  95. 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.

    Google Scholar 

  96. Wang, X. B.; You, N.; Lan, F. Q.; Fu, P.; Cui, Z.; Pang, X. C.; Liu, M. Y.; Zhao, Q. X. Facile synthesis of size–tunable superparamagnetic/polymeric core/shell nanoparticles by metal–free atom transfer radical polymerization at ambient temperature. RSC Adv. 2017, 7, 7789–7792.

    Google Scholar 

  97. Morrison, C. $1–million price tag set for Glybera gene therapy. Nat. Biotechnol. 2015, 33, 217–218.

    Google Scholar 

  98. Hoggatt, J. Gene therapy for “bubble boy” disease. Cell 2016, 166, 263.

    Google Scholar 

  99. Park, N.; Kahn, J. S.; Rice, E. J.; Hartman, M. R.; Funabashi, H.; Xu, J. F.; Um, S. H.; Luo, D. High–yield cell–free protein production from P–gel. Nat. Protoc. 2009, 4, 1759–1770.

    Google Scholar 

  100. Klinman, D. M. Immunotherapeutic uses of CpG oligodeoxynucleotides. Nat. Rev. Immunol. 2004, 4, 249–259.

    Google Scholar 

  101. Latz, E.; Verma, A.; Visintin, A.; Gong, M.; Sirois, C. M.; Klein, D. C. G.; Monks, B. G.; McKnight, C. J.; Lamphier, M. S.; Duprex, W. P. et al. Ligand–induced conformational changes allosterically activate Toll–like receptor 9. Nat. Immunol. 2007, 8, 772–779.

    Google Scholar 

Download references

Acknowledgements

This work is supported by the National Natural Science Foundation of China (Nos. 21573051, 21708004, and 51761145044), Sience Fund of Creative Research Groups of the National Natural Science Foundation of China (No. 21721002), the National Basic Research Program of China (No. 2016YFA0201601), Beijing Municipal Science & Technology Commission (No. Z161100000116036), Key Research Program of Frontier Sciences, CAS, Grant QYZDB-SSW-SLH029, CAS Interdisciplinary Innovation Team, and K. C. Wong Education Foundation.

Author information

Authors and Affiliations

  1. CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190, China

    Jianbing Liu, Zhengang Wang, Shuai Zhao & Baoquan Ding

  2. University of Chinese Academy of Sciences, Beijing, 100049, China

    Shuai Zhao & Baoquan Ding

Authors
  1. Jianbing Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhengang Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shuai Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Baoquan Ding
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Baoquan Ding.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, J., Wang, Z., Zhao, S. et al. Multifunctional nucleic acid nanostructures for gene therapies. Nano Res. 11, 5017–5027 (2018). https://doi.org/10.1007/s12274-018-2093-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12274-018-2093-x

Keywords

Search

Navigation