Abstract
Both DNA and RNA nanostructures show exceptional programmability, modularity, and self-assembly ability. Using DNA or RNA molecules it is possible to assemble monodisperse particles that are homogeneous in size and shape and with identical positioning of surface modifications. For therapeutic applications such nanoparticles are of particular interest as they can be tailored to target cells and reduce unwanted side effects due to particle heterogeneity. Recently, DNA and RNA nanostructures have demonstrated this potential by delivery of drugs to specific cells in vitro and in vivo. This has launched an increasing interest to engineer-defined DNA and RNA vehicles for drug delivery. However, before this can be realized, key challenges must be overcome including structure integrity, efficient cell targeting, and drug release. The tunable nature of DNA and RNA assemblies allows for thorough investigations into various structural and functional features, which can address these challenges. To facilitate the synthesis process novel methods enable the construction of sophisticated structures and attachment of relevant functionalities. In this chapter we will discuss the state-of-the-art molecular designs and approaches to harness and use DNA and RNA nanostructures in drug delivery.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Afonin KA, Bindewald E, Yaghoubian AJ et al (2010) In vitro assembly of cubic RNA-based scaffolds designed in silico. Nat Nanotechnol 5:676–682
Afonin KA, Grabow WW, Walker FM et al (2011) Design and self-assembly of siRNA-functionalized RNA nanoparticles for use in automated nanomedicine. Nat Protoc 6:2022–2034
Afonin KA, Kireeva M, Grabow WW et al (2012) Co-transcriptional assembly of chemically modified RNA nanoparticles functionalized with siRNAs. Nano Lett 12:5192–5195
Andersen FF, Knudsen B, Oliveira CLP et al (2008) Assembly and structural analysis of a covalently closed nano-scale DNA cage. Nucleic Acids Res 36:1113–1119
Andersen ES, Dong M, Nielsen MM et al (2009) Self-assembly of a nanoscale DNA box with a controllable lid. Nature 459:73–76
Bazile D, Prud’homme C, Bassoullet MT et al (1995) Stealth Me.PEG-PLA nanoparticles avoid uptake by the mononuclear phagocytes system. J Pharm Sci 84:493–498
Bhatia D, Surana S, Chakraborty S et al (2011) A synthetic icosahedral DNA-based host-cargo complex for functional in vivo imaging. Nat Commun 2:339
Bramsen JB (2011) Chemical modification of small interfering RNA. Methods Mol Biol 721:77–103
Chen J, Seeman N (1991) Synthesis from DNA of a molecule with the connectivity of a cube. Nature 350:631–633
Chen C, Sheng S, Shao Z et al (2000) A dimer as a building block in assembling RNA. A hexamer that gears bacterial virus phi29 DNA-translocating machinery. J Biol Chem 275:17510–17516
Chworos A, Severcan I, Koyfman AY et al (2004) Building programmable jigsaw puzzles with RNA. Science 306:2068–2072
Clemens MJ, Elia A (1997) The double-stranded RNA-dependent protein kinase PKR: structure and function. J Interferon Cytokine Res 17:503–524
Conway JW, McLaughlin CK, Castor KJ et al (2013) DNA nanostructure serum stability: greater than the sum of its parts. Chem Commun (Camb) 49:1172–1174
Davis ME, Zuckerman JE, Choi CHJ et al (2010) Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles. Nature 464:1067–1070
Delebecque CJ, Lindner AB, Silver P et al (2011) Organization of intracellular reactions with rationally designed RNA assemblies. Science 333:470–474
Diebold SS, Kaisho T, Hemmi H et al (2004) Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science 303:1529–1531
Dietz H, Douglas SM, Shih WM (2009) Folding DNA into twisted and curved nanoscale shapes. Science 325:725–730
Dill K, MacCallum JL (2012) The protein-folding problem, 50 years on. Science 338:1042–1046
Dinauer N, Balthasar S, Weber C et al (2005) Selective targeting of antibody-conjugated nanoparticles to leukemic cells and primary T-lymphocytes. Biomaterials 26:5898–5906
Douglas SM, Dietz H, Liedl T et al (2009a) Self-assembly of DNA into nanoscale three-dimensional shapes. Nature 459:414–418
Douglas SM, Marblestone AH, Teerapittayanon S et al (2009b) Rapid prototyping of 3D DNA-origami shapes with caDNAno. Nucleic Acids Res 37:5001–5006
Douglas SM, Bachelet I, Church GM (2012) A logic-gated nanorobot for targeted transport of molecular payloads. Science 335:831–834
Duckworth BP, Chen Y, Wollack JW et al (2007) A universal method for the preparation of covalent protein-DNA conjugates for use in creating protein nanostructures. Angew Chem Int Ed Engl 46:8819–8822
Endo M, Yamamoto S, Tatsumi K et al (2013) RNA-templated DNA origami structures. Chem Commun (Camb) 49:2879–2881
Erben CM, Goodman RP, Turberfield AJ (2006) Single-molecule protein encapsulation in a rigid DNA cage. Angew Chem Int Ed Engl 45:7414–7417
Fishler R, Artzy-Schnirman A, Peer E et al (2012) Mixed alkanethiol monolayers on submicrometric gold patterns: a controlled platform for studying cell-ligand interactions. Nano Lett 12:4992–4996
Freier SM, Altmann KH (1997) The ups and downs of nucleic acid duplex stability: structure-stability studies on chemically-modified DNA:RNA duplexes. Nucleic Acids Res 25:4429–4443
Gao X, Cui Y, Levenson RM et al (2004) In vivo cancer targeting and imaging with semiconductor quantum dots. Nat Biotechnol 22:969–976
Goodman RP, Schaap IAT, Tardin CF et al (2005) Rapid chiral assembly of rigid DNA building blocks for molecular nanofabrication. Science 310:1661–1665
Grabow WW, Zakrevsky P, Afonin K et al (2011) Self-assembling RNA nanorings based on RNAI/II inverse kissing complexes. Nano Lett 1:878–887
Guo P, Erickson S, Anderson D (1987) A small viral RNA is required for in vitro packaging of bacteriophage phi 29 DNA. Science 236:690–694
Guo P, Zhang C, Chen C et al (1998) Inter-RNA interaction of phage phi29 pRNA to form a hexameric complex for viral DNA transportation. Mol Cell 2:149–155
Guo S, Tschammer N, Mohammed S et al (2005) Specific delivery of therapeutic RNAs to cancer cells via the dimerization mechanism of phi29 motor pRNA. Hum Gene Ther 16:1097–1109
Guo S, Huang F, Guo P (2006) Construction of folate-conjugated pRNA of bacteriophage phi29 DNA packaging motor for delivery of chimeric siRNA to nasopharyngeal carcinoma cells. Gene Ther 13:814–820
Han D, Pal S, Liu Y et al (2010) Folding and cutting DNA into reconfigurable topological nanostructures. Nat Nanotechnol 5:712–717
Han D, Pal S, Nangreave J et al (2011) DNA origami with complex curvatures in three-dimensional space. Science 332:342–346
Haque F, Shu D, Shu Y et al (2012) Ultrastable synergistic tetravalent RNA nanoparticles for targeting to cancers. Nano Today 7:245–257
He Y, Ye T, Su M et al (2008) Hierarchical self-assembly of DNA into symmetric supramolecular polyhedra. Nature 452:198–201
Hemmi H, Takeuchi O, Kawai T et al (2000) A Toll-like receptor recognizes bacterial DNA. Nature 408:740–745
Hicke BJ, Stephens AW, Gould T et al (2006) Tumor targeting by an aptamer. J Nucl Med 47:668–678
Hoeprich S, Zhou Q, Guo S et al (2003) Bacterial virus phi29 pRNA as a hammerhead ribozyme escort to destroy hepatitis B virus. Gene Ther 10:1258–1267
Högberg B, Liedl T, Shih W (2009) Folding DNA origami from a double-stranded source of scaffold. J Am Chem Soc 131:9154–9155
Hornung V, Ellegast J, Kim S et al (2006) 5′-Triphosphate RNA is the ligand for RIG-I. Science 314:994–997
Huang J, Grater SV, Corbellini F et al (2009) Impact of order and disorder in RGD nanopatterns on cell adhesion. Nano Lett 9:1111–1116
Immordino ML, Dosio F, Cattel L (2006) Stealth liposomes: review of the basic science, rationale, and clinical applications, existing and potential. Int J Nanomedicine 1:297–315
Jaeger L, Chworos A (2006) The architectonics of programmable RNA and DNA nanostructures. Curr Opin Struct Biol 16:531–543
Jaeger L, Leontis NB (2000) Tecto-RNA: one-dimensional self-assembly through tertiary interactions. Angew Chem Int Ed Engl 39:2521–2524
Jaeger L, Westhof E, Leontis NB (2001) TectoRNA: modular assembly units for the construction of RNA nano-objects. Nucleic Acids Res 29:455–463
Jahn K, Tørring T, Voigt NV et al (2011) Functional patterning of DNA origami by parallel enzymatic modification. Bioconjug Chem 22:819–823
Jiang Q, Song C, Nangreave J et al (2012) DNA origami as a carrier for circumvention of drug resistance. J Am Chem Soc 134:13396–13403
Karkare S, Bhatnagar D (2006) Promising nucleic acid analogs and mimics: characteristic features and applications of PNA, LNA, and morpholino. Appl Microbiol Biotechnol 71:575–586
Ke Y, Sharma J, Liu M et al (2009) Scaffolded DNA origami of a DNA tetrahedron molecular container. Nano Lett 9:2445–2447
Ke Y, Ong LL, Shih WM et al (2012) Three-dimensional structures self-assembled from DNA bricks. Science 338:1177–1183
Khaled A, Guo S, Li F et al (2005) Controllable self-assembly of nanoparticles for specific delivery of multiple therapeutic molecules to cancer cells using RNA nanotechnology. Nano Lett 5:1797–1808
Kim K-R, Kim D-R, Lee T et al (2013) Drug delivery by a self-assembled DNA tetrahedron for overcoming drug resistance in breast cancer cells. Chem Commun (Camb) 5:3–5
King NP, Sheffler W, Sawaya MR et al (2012) Computational design of self-assembling protein nanomaterials with atomic level accuracy. Science 336:1171–1174
Ko S, Liu H, Chen Y et al (2008) DNA nanotubes as combinatorial vehicles for cellular delivery. Biomacromolecules 9:3039–3043
Ko SH, Su M, Zhang C et al (2010) Synergistic self-assembly of RNA and DNA molecules. Nat Chem 2:1050–1055
Koga N, Tatsumi-Koga R, Liu G et al (2012) Principles for designing ideal protein structures. Nature 491:222–227
Krishnan Y, Bathe M (2012) Designer nucleic acids to probe and program the cell. Trends Cell Biol 22:624–633
Kuzuya A, Komiyama M (2009) Design and construction of a box-shaped 3D-DNA origami. Chem Commun (Camb) 28:4182–4184
Lee H, Lytton-Jean AKR, Chen Y et al (2012) Molecularly self-assembled nucleic acid nanoparticles for targeted in vivo siRNA delivery. Nat Nanotechnol 7:389–393
Liedl T, Högberg B, Tytell J et al (2010) Self-assembly of three-dimensional prestressed tensegrity structures from DNA. Nat Nanotechnol 5:520–524
Liu X, Xu Y, Yu T et al (2012) A DNA nanostructure platform for directed assembly of synthetic vaccines. Nano Lett 12:4254–4259
Lönnberg H (2009) Solid-phase synthesis of oligonucleotide conjugates useful for delivery and targeting of potential nucleic acid therapeutics. Bioconjug Chem 20:1065–1094
Low PS, Henne W, Doorneweerd DD (2008) Discovery and development of folic-acid-based receptor targeting for imaging and therapy of cancer and inflammatory diseases. Acc Chem Res 41:120–129
Mastroianni AJ, Claridge S, Alivisatos P (2009) Pyramidal and chiral groupings of gold nanocrystals assembled using DNA scaffolds. J Am Chem Soc 131:8455–8459
Meyer R, Niemeyer CM (2011) Orthogonal protein decoration of DNA nanostructures. Small 7:3211–3218
Moghimi SM, Szebeni J (2003) Stealth liposomes and long circulating nanoparticles: critical issues in pharmacokinetics, opsonization and protein-binding properties. Prog Lipid Res 42:463–478
Nakashima Y, Abe H, Abe N et al (2011) Branched RNA nanostructures for RNA interference. Chem Commun (Camb) 47:8367–8369
Okholm AH, Nielsen JS, Vinther M et al (2014) Quantification of cellular uptake of DNA nanostructures by qPCR. Methods. http://dx.doi.org/10.1016/j.ymeth.2014.01.013
Oliveira CLP, Juul S, Jørgensen HL et al (2010) Structure of nanoscale truncated octahedral DNA cages: variation of single-stranded linker regions and influence on assembly yields. ACS Nano 4:1367–1376
Peer D, Karp JM, Hong S et al (2007) Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol 2:751–760
Pinheiro AV, Han D, Shih WM et al (2011) Challenges and opportunities for structural DNA nanotechnology. Nat Nanotechnol 6:763–772
Rinker S, Ke Y, Liu Y et al (2008) Self-assembled DNA nanostructures for distance-dependent multivalent ligand-protein binding. Nat Nanotechnol 3:418–422
Rossi JJ (2005) RNAi therapeutics: SNALPing siRNAs in vivo. Gene Ther 13:583–584
Rothemund PWK (2006) Folding DNA to create nanoscale shapes and patterns. Nature 440:297–302
Saccà B, Niemeyer CM (2011) Functionalization of DNA nanostructures with proteins. Chem Soc Rev 40:5910–5921
Said H, Schüller VJ, Eber FJ et al (2013) M1.3–a small scaffold for DNA origami. Nanoscale 5:284–290
Schüller VJ, Heidegger S, Sandholzer N et al (2011) Cellular immunostimulation by CpG-sequence-coated DNA origami structures. ACS Nano 5:9696–9702
Seeman NC (1982) Nucleic acid junctions and lattices. J Theor Biol 99:237–247
Severcan I, Geary C, Verzemnieks E et al (2009) Square-shaped RNA particles from different RNA folds. Nano Lett 9:1270–1277
Severcan I, Geary C, Chworos A et al (2010) A polyhedron made of tRNAs. Nat Chem 2:772–779
Sharma J, Chhabra R, Andersen CS et al (2008) Toward reliable gold nanoparticle patterning on self-assembled DNA nanoscaffold. J Am Chem Soc 130:7820–7821
Shen W, Zhong H, Neff D et al (2009) NTA directed protein nanopatterning on DNA origami nanoconstructs. J Am Chem Soc 131:6660–6661
Shih WM, Quispe JD, Joyce GF (2004) A 1.7-kilobase single-stranded DNA that folds into a nanoscale octahedron. Nature 427:618–621
Shu D, Huang LP, Hoeprich S et al (2003) Construction of phi29 DNA-packaging RNA monomers, dimers, and trimers with variable sizes and shapes as potential parts for nanodevices. J Nanosci Nanotechnol 3:295–302
Shu D, Shu Y, Haque F et al (2011) Thermodynamically stable RNA three-way junction for constructing multifunctional nanoparticles for delivery of therapeutics. Nat Nanotechnol 6:658–667
Smith D, Schüller V, Engst C et al (2013) Nucleic acid nanostructures for biomedical applications. Nanomedicine 8:105–121
Sørensen RS, Okholm AH, Schaffert D et al (2013) Enzymatic ligation of large biomolecules to DNA. ACS Nano 7:1–16
Tørring T, Voigt NV, Nangreave J et al (2011) DNA origami: a quantum leap for self-assembly of complex structures. Chem Soc Rev 40:5636–5646
Varkouhi AK, Scholte M, Storm G et al (2011) Endosomal escape pathways for delivery of biologicals. J Control Release 151:220–228
Walsh AS, Yin H, Erben CM et al (2011) DNA cage delivery to mammalian cells. ACS Nano 5:5427–5432
Wei B, Dai M, Yin P (2012) Complex shapes self-assembled from single-stranded DNA tiles. Nature 485:623–626
Westhof E, Masquida B, Jaeger L (1996) RNA tectonics: towards RNA design. Fold Des 1:R78–R88
Williams BR, Lund K, Liu Y et al (2007) Self-assembled peptide nanoarrays: an approach to studying protein-protein interactions. Angew Chem Int Ed Engl 46:3051–3054
Wilner OI, Willner I (2012) Functionalized DNA nanostructures. Chem Rev 112:2528–2556
Wilner O, Weizmann Y, Gill R (2009) Enzyme cascades activated on topologically programmed DNA scaffolds. Nat Nanotechnol 4:249–254
Win MN, Smolke CD (2007) A modular and extensible RNA-based gene-regulatory platform for engineering cellular function. Proc Natl Acad Sci U S A 104:14283–14288
Yan H, Park SH, Finkelstein G et al (2003) DNA-templated self-assembly of protein arrays and highly conductive nanowires. Science 301:1882–1884
Yang Y, Han D, Nangreave J et al (2012) DNA origami with double-stranded DNA as a unified scaffold. ACS Nano 6:8209–8215
Yingling YG, Shapiro B (2007) Computational design of an RNA hexagonal nanoring and an RNA nanotube. Nano Lett 7:2328–2334
Zadegan RM, Jepsen MDE, Thomsen KE et al (2012) Construction of a 4 zeptoliters switchable 3D DNA box origami. ACS Nano 6:10050–10053
Zhang Y, Seeman NC (1994) Construction of a DNA-truncated octahedron. J Am Chem Soc 116:1661–1669
Zhang L, Gu FX, Chan JM et al (2008) Nanoparticles in medicine: therapeutic applications and developments. Clin Pharmacol Ther 83:761–769
Zhang HM, Su Y, Guo S et al (2009) Targeted delivery of anti-coxsackievirus siRNAs using ligand-conjugated packaging RNAs. Antiviral Res 83:307–316
Zhang H, Chao J, Pan D et al (2012) Folding super-sized DNA origami with scaffold strands from long-range PCR. Chem Commun (Camb) 48:6405–6407
Zhao Z, Liu Y, Yan H (2011) Organizing DNA origami tiles into larger structures using preformed scaffold frames. Nano Lett 11:2997–3002
Zhao Y-X, Shaw A, Zeng X et al (2012) DNA origami delivery system for cancer therapy with tunable release properties. ACS Nano 6:8684–8691
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Okholm, A.H., Schaffert, D., Kjems, J. (2014). Towards Defined DNA and RNA Delivery Vehicles Using Nucleic Acid Nanotechnology. In: Erdmann, V., Markiewicz, W., Barciszewski, J. (eds) Chemical Biology of Nucleic Acids. RNA Technologies. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-54452-1_18
Download citation
DOI: https://doi.org/10.1007/978-3-642-54452-1_18
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-54451-4
Online ISBN: 978-3-642-54452-1
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)