Skip to main content

Multifunctional Nanoscale Delivery Systems for Nucleic Acids

  • Chapter
  • First Online:
Engineering in Translational Medicine
  • 2562 Accesses

Abstract

Nanoscale systems have emerged in the past two decades as attractive platforms for delivering nucleic acids in vivo while performing other therapeutic or diagnostic functions, though their full potential for improving human health has yet to be realized in the clinic. Bioengineering techniques have been crucial for modifying and optimizing synthetic and viral delivery systems to include drugs, imaging agents and targeting moieties as well as reducing toxicity effects and increasing delivery efficiency and specificity. Directed delivery technologies can complement these nanoscale systems to localize therapy in vivo. The use of nucleic acid analogs can also enhance therapeutic efficacy under ideal circumstances. This chapter will review some of the recent developments in RNA and DNA delivery research with a focus on progress toward human therapies, the challenges that have been encountered, and the engineering approaches that have been employed. In addition to on-going work on the optimization of delivery systems, three challenging areas are identified: (1) the development of heterogeneous, three-dimensional microenvironments for testing delivery systems, (2) imaging approaches to understand the dynamic interactions of systems from administration through delivery in the human population, and (3) development and translation of directed technologies capable of enhancing delivery in a clinical setting and producing a sustained therapeutic effect.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Edelstein M (2012) Gene therapy clinical trials worldwide. J Gene Med. http://www.abedia.com/wiley/vectors.php. Accessed 21 Jan 2013

  2. Burnett JC, Rossi JJ, Tiemann K (2011) Current progress of siRNA/shRNA therapeutics in clinical trials. Biotechnol J 6:1130–1146. doi:10.1002/biot.201100054

    Google Scholar 

  3. Jiao S, Williams P, Berg R et al (1992) Direct gene transfer into nonhuman primate myofibers in vivo. Hum Gene Ther 3:21–33. doi:10.1089/hum.1992.3.1-21

    Google Scholar 

  4. Ardehali A, Fyfe A, Laks H et al (1995) Direct gene transfer into donor hearts at the time of harvest. J Thorac Cardiovasc Surg 109:716–720. doi:10.1016/S0022-5223(95)70353-5

    Google Scholar 

  5. Vile R, Hart I (1993) In vitro and in vivo targeting of gene expression to melanoma cells. Cancer Res 53:962–967

    Google Scholar 

  6. Khatri N, Rathi M, Baradia D et al (2012) In vivo delivery aspects of miRNA, shRNA and siRNA. Crit Rev Ther Drug Carrier Syst 29:487–527

    Google Scholar 

  7. Inoue T, Sugimoto M, Sakurai T et al (2007) Modulation of scratching behavior by silencing an endogenous cyclooxygenase-1 gene in the skin through the administration of siRNA. J Gene Med 9:994–1001. doi:10.1002/jgm.1091

    Google Scholar 

  8. Bitko V, Musiyenko A, Shulyayeva O, Barik S (2005) Inhibition of respiratory viruses by nasally administered siRNA. Nat Med 11:50–55. doi:10.1038/nm1164

    Google Scholar 

  9. DiFiglia M, Sena-Esteves M, Chase K et al (2007) Therapeutic silencing of mutant huntingtin with siRNA attenuates striatal and cortical neuropathology and behavioral deficits. Proc Natl Acad Sci USA 104:17204–17209. doi:10.1073/pnas.0708285104

    Google Scholar 

  10. Sinn PL, Anthony RM, McCray PB Jr (2011) Genetic therapies for cystic fibrosis lung disease. Hum Mol Genet 20:R79–R86. doi:10.1093/hmg/ddr104

    Google Scholar 

  11. Kamimura K, Suda T, Zhang G, Liu D (2011) Advances in gene delivery systems. Pharmaceut Med 25:293–306. doi:10.2165/11594020-000000000-00000

    Google Scholar 

  12. Maetzig T, Galla M, Baum C, Schambach A (2011) Gammaretroviral vectors: biology, technology and application. Viruses 3:677–713. doi:10.3390/v3060677

    Google Scholar 

  13. Coffin JMJM, Hughes SHSH, Varmus HEHE (1997) Retroviruses. Cold Spring Harbor Laboratory Press, Cold Spring Harbor

    Google Scholar 

  14. Hu WS, Pathak VK (2000) Design of retroviral vectors and helper cells for gene therapy. Pharmacol Rev 52:493–511

    Google Scholar 

  15. Lewis P, Hensel M, Emerman M (1992) Human immunodeficiency virus infection of cells arrested in the cell cycle. EMBO J 11:3053–3058

    Google Scholar 

  16. Lee C-L, Dang J, Joo K-I, Wang P (2011) Engineered lentiviral vectors pseudotyped with a CD4 receptor and a fusogenic protein can target cells expressing HIV-1 envelope proteins. Virus Res 160:340–350. doi:10.1016/j.virusres.2011.07.010

    Google Scholar 

  17. Dimitrov DS (1997) How do viruses enter cells? The HIV coreceptors teach us a lesson of complexity. Cell 91:721–730

    Google Scholar 

  18. Moore JP (1997) Coreceptors: implications for HIV pathogenesis and therapy. Science 276:51–52

    Google Scholar 

  19. Cockrell AS, Kafri T (2007) Gene delivery by lentivirus vectors. Mol Biotechnol 36:184–204

    Google Scholar 

  20. Miller DG, Adam MA, Miller AD (1990) Gene transfer by retrovirus vectors occurs only in cells that are actively replicating at the time of infection. Mol Cell Biol 10:4239–4242

    Google Scholar 

  21. Durand S, Cimarelli A (2011) The inside out of lentiviral vectors. Viruses 3:132–159. doi:10.3390/v3020132

    Google Scholar 

  22. Pfeifer A, Ikawa M, Dayn Y, Verma IM (2002) Transgenesis by lentiviral vectors: lack of gene silencing in mammalian embryonic stem cells and preimplantation embryos. Proc Natl Acad Sci USA 99:2140–2145. doi:10.1073/pnas.251682798

    Google Scholar 

  23. Bahrami S, Pedersen FS (2009) Viral technology for delivery of nucleic acids. In: Jorgensen L, Nielsen HM (eds) Delivery technologies for biopharmaceuticals. Wiley, Chichester, pp 93–112

    Google Scholar 

  24. Cavazzana-Calvo M (2000) Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease. Science 288:669–672. doi:10.1126/science.288.5466.669

    Google Scholar 

  25. Mátrai J, Chuah MKL, VandenDriessche T (2010) Recent advances in lentiviral vector development and applications. Mol Ther 18:477–490. doi:10.1038/mt.2009.319

    Google Scholar 

  26. Izmiryan A, Basmaciogullari S, Henry A et al (2011) Efficient gene targeting mediated by a lentiviral vector-associated meganuclease. Nucleic Acids Res 39:7610–7619. doi:10.1093/nar/gkr524

    Google Scholar 

  27. Sarkis C, Philippe S, Mallet J, Serguera C (2008) Non-integrating lentiviral vectors. Curr Gene Ther 8:430–437

    Google Scholar 

  28. Nightingale SJ, Hollis RP, Pepper KA et al (2006) Transient gene expression by nonintegrating lentiviral vectors. Mol Ther 13:1121–1132. doi:10.1016/j.ymthe.2006.01.008

    Google Scholar 

  29. Yáñez-Muñoz RJ, Balaggan KS, MacNeil A et al (2006) Effective gene therapy with nonintegrating lentiviral vectors. Nat Med 12:348–353. doi:10.1038/nm1365

    Google Scholar 

  30. Barquinero J, Eixarch H, Pérez-Melgosa M (2004) Retroviral vectors: new applications for an old tool. Gene Ther 11(Suppl 1):S3–S9. doi:10.1038/sj.gt.3302363

    Google Scholar 

  31. Daniel R, Smith JA (2008) Integration site selection by retroviral vectors: molecular mechanism and clinical consequences. Hum Gene Ther 19:557–568. doi:10.1089/hum.2007.148

    Google Scholar 

  32. Culver K, Cornetta K, Morgan R et al (1991) Lymphocytes as cellular vehicles for gene therapy in mouse and man. Proc Natl Acad Sci USA 88:3155–3159

    Google Scholar 

  33. Rosenberg SA, Aebersold P, Cornetta K et al (1990) Gene transfer into humans–immunotherapy of patients with advanced melanoma, using tumor-infiltrating lymphocytes modified by retroviral gene transduction. N Engl J Med 323:570–578. doi:10.1056/NEJM199008303230904

    Google Scholar 

  34. Blaese RM, Culver KW, Miller AD et al (1995) T lymphocyte-directed gene therapy for ADA-SCID: initial trial results after 4 years. Science 270:475–480

    Google Scholar 

  35. Stone D (2010) Novel viral vector systems for gene therapy. Viruses 2:1002–1007. doi:10.3390/v2041002

    Google Scholar 

  36. D’Costa J, Mansfield SG, Humeau LM (2009) Lentiviral vectors in clinical trials: current status. Curr Opin Mol Ther 11:554–564

    Google Scholar 

  37. Schambach A, Baum C (2008) Clinical application of lentiviral vectors: concepts and practice. Curr Gene Ther 8:474–482

    Google Scholar 

  38. Bank A, Dorazio R, Leboulch P (2005) A phase I/II clinical trial of beta-globin gene therapy for beta-thalassemia. Ann N Y Acad Sci 1054:308–316. doi:10.1196/annals.1345.007

    Google Scholar 

  39. Pedersen FS, Pyrz M, Duch M (2011) Retroviral replication. Encyclopedia of Life Sciences. doi:10.1002/9780470015902.a0000430.pub3

  40. Muralidhar S, Becerra SP, Rose JA (1994) Site-directed mutagenesis of adeno-associated virus type 2 structural protein initiation codons: effects on regulation of synthesis and biological activity. J Virol 68:170–176

    Google Scholar 

  41. Girod A, Wobus CE, Zádori Z et al (2002) The VP1 capsid protein of adeno-associated virus type 2 is carrying a phospholipase A2 domain required for virus infectivity. J Gen Virol 83:973–978

    Google Scholar 

  42. Zádori Z, Szelei J, Lacoste MC et al (2001) A viral phospholipase A2 is required for parvovirus infectivity. Dev Cell 1:291–302

    Google Scholar 

  43. Grieger JC, Samulski RJ (2005) Packaging capacity of adeno-associated virus serotypes: impact of larger genomes on infectivity and postentry steps. J Virol 79:9933–9944. doi:10.1128/JVI.79.15.9933-9944.2005

    Google Scholar 

  44. McCarty DM, Young SM Jr, Samulski RJ (2004) Integration of adeno-associated virus (AAV) and recombinant AAV vectors. Annu Rev Genet 38:819–845. doi:10.1146/annurev.genet.37.110801.143717

    Google Scholar 

  45. Allocca M, Doria M, Petrillo M et al (2008) Serotype-dependent packaging of large genes in adeno-associated viral vectors results in effective gene delivery in mice. J Clin Invest 118:1955–1964. doi:10.1172/JCI34316

    Google Scholar 

  46. Gao G, Vandenberghe LH, Wilson JM (2005) New recombinant serotypes of AAV vectors. Curr Gene Ther 5:285–297

    Google Scholar 

  47. Taymans J-M, Vandenberghe LH, Haute CVD et al (2007) Comparative analysis of adeno-associated viral vector serotypes 1, 2, 5, 7, and 8 in mouse brain. Hum Gene Ther 18:195–206. doi:10.1089/hum.2006.178

    Google Scholar 

  48. Carter BJ (2005) Adeno-associated virus vectors in clinical trials. Hum Gene Ther 16:541–550. doi:10.1089/hum.2005.16.541

    Google Scholar 

  49. Bennett J (2006) Commentary: an aye for eye gene therapy. Hum Gene Ther 17:177–179. doi:10.1089/hum.2006.17.177

    Google Scholar 

  50. LeWitt PA, Rezai AR, Leehey MA et al (2011) AAV2-GAD gene therapy for advanced Parkinson’s disease: a double-blind, sham-surgery controlled, randomised trial. Lancet Neurol 10:309–319. doi:10.1016/S1474-4422(11)70039-4

    Google Scholar 

  51. Bainbridge JWB, Smith AJ, Barker SS et al (2008) Effect of gene therapy on visual function in Leber’s congenital amaurosis. N Engl J Med 358:2231–2239. doi:10.1056/NEJMoa0802268

    Google Scholar 

  52. Zabner J, Fasbender AJ, Moninger T et al (1995) Cellular and molecular barriers to gene transfer by a cationic lipid. J Biol Chem 270:18997–19007

    Google Scholar 

  53. Ng CP, Pun SH (2008) A perfusable 3D cell-matrix tissue culture chamber for in situ evaluation of nanoparticle vehicle penetration and transport. Biotechnol Bioeng 99:1490–1501. doi:10.1002/bit.21698

    Google Scholar 

  54. Ye Z, Houssein HSH, Mahato RI (2007) Bioconjugation of oligonucleotides for treating liver fibrosis. Oligonucleotides 17:349–404. doi:10.1089/oli.2007.0097

    Google Scholar 

  55. Mo RH, Zaro JL, Shen W-C (2012) Comparison of cationic and amphipathic cell penetrating peptides for siRNA delivery and efficacy. Mol Pharm 9:299–309. doi:10.1021/mp200481g

    Google Scholar 

  56. Shiraishi T, Nielsen PE (2011) Peptide nucleic acid (PNA) cell penetrating peptide (CPP) conjugates as carriers for cellular delivery of antisense oligomers. Artif DNA PNA XNA 2:90–99

    Google Scholar 

  57. Sanders WS, Johnston CI, Bridges SM et al (2011) Prediction of cell penetrating peptides by support vector machines. PLoS Comput Biol 7:e1002101. doi:10.1371/journal.pcbi.1002101

    Google Scholar 

  58. Bidwell GL 3rd, Raucher D (2010) Cell penetrating elastin-like polypeptides for therapeutic peptide delivery. Adv Drug Deliv Rev 62:1486–1496. doi:10.1016/j.addr.2010.05.003

    Google Scholar 

  59. Puri A, Loomis K, Smith B et al (2009) Lipid-based nanoparticles as pharmaceutical drug carriers: from concepts to clinic. Crit Rev Ther Drug Carrier Syst 26:523–580

    Google Scholar 

  60. Semple SC, Akinc A, Chen J et al (2010) Rational design of cationic lipids for siRNA delivery. Nat Biotechnol 28:172–176. doi:10.1038/nbt.1602

    Google Scholar 

  61. Chapter 17—Engineering cationic liposome s… [Methods Enzymol 464:343–454 (2009). doi:10.1016/S0076-6879(09)64017-9]—PubMed—NCBI. http://www.ncbi.nlm.nih.gov/pubmed/19903563. Accessed 4 Feb 2013

  62. Kenjo E, Asai T, Yonenaga N et al (2013) Systemic delivery of small interfering RNA by use of targeted polycation liposomes for cancer therapy. Biol Pharm Bull 36:287–291

    Google Scholar 

  63. Zuhorn IS, Bakowsky U, Polushkin E et al (2005) Nonbilayer phase of lipoplex-membrane mixture determines endosomal escape of genetic cargo and transfection efficiency. Mol Ther 11:801–810. doi:10.1016/j.ymthe.2004.12.018

    Google Scholar 

  64. Guo X, Szoka FC Jr (2003) Chemical approaches to triggerable lipid vesicles for drug and gene delivery. Acc Chem Res 36:335–341. doi:10.1021/ar9703241

    Google Scholar 

  65. Stover TC, Sharma A, Robertson GP, Kester M (2005) Systemic delivery of liposomal short-chain ceramide limits solid tumor growth in murine models of breast adenocarcinoma. Clin Cancer Res 11:3465–3474. doi:10.1158/1078-0432.CCR-04-1770

    Google Scholar 

  66. Giddam AK, Zaman M, Skwarczynski M, Toth I (2012) Liposome-based delivery system for vaccine candidates: constructing an effective formulation. Nanomedicine (Lond) 7:1877–1893. doi:10.2217/nnm.12.157

    Google Scholar 

  67. Lam AP, Dean DA (2010) Progress and prospects: nuclear import of nonviral vectors. Gene Ther 17:439–447. doi:10.1038/gt.2010.31

    Google Scholar 

  68. Wu Z-W, Chien C-T, Liu C-Y et al (2012) Recent progress in copolymer-mediated siRNA delivery. J Drug Target 20:551–560. doi:10.3109/1061186X.2012.699057

    Google Scholar 

  69. Lee S-Y, Huh MS, Lee S et al (2010) Stability and cellular uptake of polymerized siRNA (poly-siRNA)/polyethylenimine (PEI) complexes for efficient gene silencing. J Control Release 141:339–346. doi:10.1016/j.jconrel.2009.10.007

    Google Scholar 

  70. Kim SW, Kim NY, Choi YB et al (2010) RNA interference in vitro and in vivo using an arginine peptide/siRNA complex system. J Control Release 143:335–343. doi:10.1016/j.jconrel.2010.01.009

    MathSciNet  Google Scholar 

  71. Guo J, Cheng WP, Gu J et al (2012) Systemic delivery of therapeutic small interfering RNA using a pH-triggered amphiphilic poly-l-lysine nanocarrier to suppress prostate cancer growth in mice. Eur J Pharm Sci 45:521–532. doi:10.1016/j.ejps.2011.11.024

    Google Scholar 

  72. Panyam J, Labhasetwar V (2003) Biodegradable nanoparticles for drug and gene delivery to cells and tissue. Adv Drug Deliv Rev 55:329–347

    Google Scholar 

  73. He C, Yin L, Tang C, Yin C (2013) Multifunctional polymeric nanoparticles for oral delivery of TNF-α siRNA to macrophages. Biomaterials. doi:10.1016/j.biomaterials.2013.01.033

    Google Scholar 

  74. Woodrow KA, Cu Y, Booth CJ et al (2009) Intravaginal gene silencing using biodegradable polymer nanoparticles densely loaded with small-interfering RNA. Nat Mater 8:526–533. doi:10.1038/nmat2444

    Google Scholar 

  75. Bamrungsap S, Zhao Z, Chen T et al (2012) Nanotechnology in therapeutics: a focus on nanoparticles as a drug delivery system. Nanomedicine (Lond) 7:1253–1271. doi:10.2217/nnm.12.87

    Google Scholar 

  76. Pérez-Martínez FC, Ocaña AV, Pérez-Carrión MD, Ceña V (2012) Dendrimers as vectors for genetic material delivery to the nervous system. Curr Med Chem 19:5101–5108

    Google Scholar 

  77. Albertazzi L, Gherardini L, Brondi M et al (2013) In vivo distribution and toxicity of PAMAM dendrimers in the central nervous system depend on their surface chemistry. Mol Pharm 10:249–260. doi:10.1021/mp300391v

    Google Scholar 

  78. Liu Y, Huang R, Han L et al (2009) Brain-targeting gene delivery and cellular internalization mechanisms for modified rabies virus glycoprotein RVG29 nanoparticles. Biomaterials 30:4195–4202. doi:10.1016/j.biomaterials.2009.02.051

    Google Scholar 

  79. Yu T, Liu X, Bolcato-Bellemin A-L et al (2012) An amphiphilic dendrimer for effective delivery of small interfering RNA and gene silencing in vitro and in vivo. Angew Chem Int Ed Engl 51:8478–8484. doi:10.1002/anie.201203920

    Google Scholar 

  80. Xie J, Lee S, Chen X (2010) Nanoparticle-based theranostic agents. Adv Drug Deliv Rev 62:1064–1079. doi:10.1016/j.addr.2010.07.009

    Google Scholar 

  81. Medarova Z, Pham W, Farrar C et al (2007) In vivo imaging of siRNA delivery and silencing in tumors. Nat Med 13:372–377. doi:10.1038/nm1486

    Google Scholar 

  82. Cormode DP, Skajaa GO, Delshad A et al (2011) A versatile and tunable coating strategy allows control of nanocrystal delivery to cell types in the liver. Bioconjug Chem 22:353–361. doi:10.1021/bc1003179

    Google Scholar 

  83. Taratula O, Garbuzenko O, Savla R et al (2011) Multifunctional nanomedicine platform for cancer specific delivery of siRNA by superparamagnetic iron oxide nanoparticles-dendrimer complexes. Curr Drug Deliv 8:59–69

    Google Scholar 

  84. Derfus AM, Chen AA, Min D-H et al (2007) Targeted quantum dot conjugates for siRNA delivery. Bioconjug Chem 18:1391–1396. doi:10.1021/bc060367e

    Google Scholar 

  85. Gao X, Cui Y, Levenson RM et al (2004) In vivo cancer targeting and imaging with semiconductor quantum dots. Nat Biotechnol 22:969–976. doi:10.1038/nbt994

    Google Scholar 

  86. Zrazhevskiy P, Sena M, Gao X (2010) Designing multifunctional quantum dots for bioimaging, detection, and drug delivery. Chem Soc Rev 39:4326–4354. doi:10.1039/b915139g

    Google Scholar 

  87. Zhang P, Liu W (2010) ZnO QD@PMAA-co-PDMAEMA nonviral vector for plasmid DNA delivery and bioimaging. Biomaterials 31:3087–3094. doi:10.1016/j.biomaterials.2010.01.007

    Google Scholar 

  88. Radu DR, Lai C-Y, Jeftinija K et al (2004) A polyamidoamine dendrimer-capped mesoporous silica nanosphere-based gene transfection reagent. J Am Chem Soc 126:13216–13217. doi:10.1021/ja046275m

    Google Scholar 

  89. Hom C, Lu J, Liong M et al (2010) Mesoporous silica nanoparticles facilitate delivery of siRNA to shutdown signaling pathways in mammalian cells. Small 6:1185–1190. doi:10.1002/smll.200901966

    Google Scholar 

  90. Meng H, Liong M, Xia T et al (2010) Engineered design of mesoporous silica nanoparticles to deliver doxorubicin and P-glycoprotein siRNA to overcome drug resistance in a cancer cell line. ACS Nano 4:4539–4550. doi:10.1021/nn100690m

    Google Scholar 

  91. Bhattarai SR, Muthuswamy E, Wani A et al (2010) Enhanced gene and siRNA delivery by polycation-modified mesoporous silica nanoparticles loaded with chloroquine. Pharm Res 27:2556–2568. doi:10.1007/s11095-010-0245-0

    Google Scholar 

  92. Meng H, Mai WX, Zhang H et al (2013) Codelivery of an optimal drug/siRNA combination using mesoporous silica nanoparticles to overcome drug resistance in breast cancer in vitro and in vivo. ACS Nano. doi:10.1021/nn3044066

    Google Scholar 

  93. Thomas M, Klibanov AM (2003) Conjugation to gold nanoparticles enhances polyethylenimine’s transfer of plasmid DNA into mammalian cells. Proc Natl Acad Sci USA 100:9138–9143. doi:10.1073/pnas.1233634100

    Google Scholar 

  94. Rosi NL, Giljohann DA, Thaxton CS et al (2006) Oligonucleotide-modified gold nanoparticles for intracellular gene regulation. Science 312:1027–1030. doi:10.1126/science.1125559

    Google Scholar 

  95. Guo S, Huang Y, Jiang Q et al (2010) Enhanced gene delivery and siRNA silencing by gold nanoparticles coated with charge-reversal polyelectrolyte. ACS Nano 4:5505–5511. doi:10.1021/nn101638u

    Google Scholar 

  96. Bonoiu AC, Bergey EJ, Ding H et al (2011) Gold nanorod–siRNA induces efficient in vivo gene silencing in the rat hippocampus. Nanomedicine (Lond) 6:617–630. doi:10.2217/nnm.11.20

    Google Scholar 

  97. Zhang X-Q, Chen M, Lam R et al (2009) Polymer-functionalized nanodiamond platforms as vehicles for gene delivery. ACS Nano 3:2609–2616. doi:10.1021/nn900865g

    Google Scholar 

  98. Zhang L, Lu Z, Zhao Q et al (2011) Enhanced chemotherapy efficacy by sequential delivery of siRNA and anticancer drugs using PEI-grafted graphene oxide. Small 7:460–464. doi:10.1002/smll.201001522

    Google Scholar 

  99. Alhaddad A, Adam M-P, Botsoa J et al (2011) Nanodiamond as a vector for siRNA delivery to Ewing sarcoma cells. Small 7:3087–3095. doi:10.1002/smll.201101193

    Google Scholar 

  100. Mohan N, Chen C-S, Hsieh H–H et al (2010) In vivo imaging and toxicity assessments of fluorescent nanodiamonds in caenorhabditis elegans. Nano Lett 10:3692–3699. doi:10.1021/nl1021909

    Google Scholar 

  101. Pantarotto D, Singh R, McCarthy D et al (2004) Functionalized carbon nanotubes for plasmid DNA gene delivery. Angew Chem Int Ed Engl 43:5242–5246. doi:10.1002/anie.200460437

    Google Scholar 

  102. McCarroll J, Baigude H, Yang C-S, Rana TM (2010) Nanotubes functionalized with lipids and natural amino acid dendrimers: a new strategy to create nanomaterials for delivering systemic RNAi. Bioconjug Chem 21:56–63. doi:10.1021/bc900296z

    Google Scholar 

  103. Yang K, Zhang S, Zhang G et al (2010) Graphene in mice: ultrahigh in vivo tumor uptake and efficient photothermal therapy. Nano Lett 10:3318–3323. doi:10.1021/nl100996u

    Google Scholar 

  104. Zhang W, Guo Z, Huang D et al (2011) Synergistic effect of chemo-photothermal therapy using PEGylated graphene oxide. Biomaterials 32:8555–8561. doi:10.1016/j.biomaterials.2011.07.071

    Google Scholar 

  105. Suda T, Liu D (2007) Hydrodynamic gene delivery: its principles and applications. Mol Ther 15:2063–2069. doi:10.1038/sj.mt.6300314

    Google Scholar 

  106. Suda T, Suda K, Liu D (2008) Computer-assisted hydrodynamic gene delivery. Mol Ther 16:1098–1104. doi:10.1038/mt.2008.66

    Google Scholar 

  107. Kamimura K, Zhang G, Liu D (2010) Image-guided, intravascular hydrodynamic gene delivery to skeletal muscle in pigs. Mol Ther 18:93–100. doi:10.1038/mt.2009.206

    Google Scholar 

  108. Mellott AJ, Forrest ML, Detamore MS (2012) Physical non-viral gene delivery methods for tissue engineering. Ann Biomed Eng. doi:10.1007/s10439-012-0678-1

    Google Scholar 

  109. Fuller DH, Loudon P, Schmaljohn C (2006) Preclinical and clinical progress of particle-mediated DNA vaccines for infectious diseases. Methods 40:86–97. doi:10.1016/j.ymeth.2006.05.022

    Google Scholar 

  110. Kis EE, Winter G, Myschik J (2012) Devices for intradermal vaccination. Vaccine 30:523–538. doi:10.1016/j.vaccine.2011.11.020

    Google Scholar 

  111. Sardesai NY, Weiner DB (2011) Electroporation delivery of DNA vaccines: prospects for success. Curr Opin Immunol 23:421–429. doi:10.1016/j.coi.2011.03.008

    Google Scholar 

  112. Littel-van Van Drunen, den Hurk S, Hannaman D (2010) Electroporation for DNA immunization: clinical application. Expert Rev Vaccines 9:503–517. doi:10.1586/erv.10.42

    Google Scholar 

  113. Daud AI, DeConti RC, Andrews S et al (2008) Phase I trial of interleukin-12 plasmid electroporation in patients with metastatic melanoma. J Clin Oncol 26:5896–5903. doi:10.1200/JCO.2007.15.6794

    Google Scholar 

  114. Broderick KE, Shen X, Soderholm J et al (2011) Prototype development and preclinical immunogenicity analysis of a novel minimally invasive electroporation device. Gene Ther 18:258–265. doi:10.1038/gt.2010.137

    Google Scholar 

  115. Yamaoka A, Guan X, Takemoto S et al (2010) Development of a novel Hsp70-based DNA vaccine as a multifunctional antigen delivery system. J Control Release 142:411–415. doi:10.1016/j.jconrel.2009.11.005

    Google Scholar 

  116. Suzuki R, Oda Y, Utoguchi N, Maruyama K (2011) Progress in the development of ultrasound-mediated gene delivery systems utilizing nano- and microbubbles. J Control Release 149:36–41. doi:10.1016/j.jconrel.2010.05.009

    Google Scholar 

  117. He Y, Bi Y, Hua Y et al (2011) Ultrasound microbubble-mediated delivery of the siRNAs targeting MDR1 reduces drug resistance of yolk sac carcinoma L2 cells. J Exp Clin Cancer Res 30:104. doi:10.1186/1756-9966-30-104

    Google Scholar 

  118. Raju BI, Leyvi E, Seip R et al (2013) Enhanced gene expression of systemically administered plasmid DNA in the liver with therapeutic ultrasound and microbubbles. IEEE Trans Ultrason Ferroelectr Freq Control 60:88–96

    Google Scholar 

  119. Liu Y, Yan J, Prausnitz MR (2012) Can ultrasound enable efficient intracellular uptake of molecules? A retrospective literature review and analysis. Ultrasound Med Biol 38:876–888. doi:10.1016/j.ultrasmedbio.2012.01.006

    Google Scholar 

  120. Cosgrove D, Harvey C (2009) Clinical uses of microbubbles in diagnosis and treatment. Med Biol Eng Comput 47:813–826. doi:10.1007/s11517-009-0434-3

    Google Scholar 

  121. Alzaraa A, Gravante G, Chung WY et al (2012) Targeted microbubbles in the experimental and clinical setting. Am J Surg 204:355–366. doi:10.1016/j.amjsurg.2011.10.024

    Google Scholar 

  122. Chorny M, Fishbein I, Yellen BB et al (2010) Targeting stents with local delivery of paclitaxel-loaded magnetic nanoparticles using uniform fields. Proc Natl Acad Sci USA 107:8346–8351. doi:10.1073/pnas.0909506107

    Google Scholar 

  123. Zheng X, Lu J, Deng L et al (2009) Preparation and characterization of magnetic cationic liposome in gene delivery. Int J Pharm 366:211–217. doi:10.1016/j.ijpharm.2008.09.019

    Google Scholar 

  124. Plank C, Zelphati O, Mykhaylyk O (2011) Magnetically enhanced nucleic acid delivery. Ten years of magnetofection-progress and prospects. Adv Drug Deliv Rev 63:1300–1331. doi:10.1016/j.addr.2011.08.002

    Google Scholar 

  125. Vogel A, Noack J, Hüttman G, Paltauf G (2005) Mechanisms of femtosecond laser nanosurgery of cells and tissues. Applied Physics B 81:1015–1047. doi:10.1007/s00340-005-2036-6

    Google Scholar 

  126. Tirlapur UK, König K (2002) Cell biology: Targeted transfection by femtosecond laser. Nature 418:290–291. doi:10.1038/418290a

    Google Scholar 

  127. Barrett LE, Sul J-Y, Takano H et al (2006) Region-directed phototransfection reveals the functional significance of a dendritically synthesized transcription factor. Nat Methods 3:455–460. doi:10.1038/nmeth885

    Google Scholar 

  128. Kohli V, Robles V, Cancela ML et al (2007) An alternative method for delivering exogenous material into developing zebrafish embryos. Biotechnol Bioeng 98:1230–1241. doi:10.1002/bit.21564

    Google Scholar 

  129. Tsampoula X, Taguchi K, Cižmár T et al (2008) Fibre based cellular transfection. Opt Express 16:17007. doi:10.1364/OE.16.017007

    Google Scholar 

  130. Menezes V, Mathew Y, Takayama K et al (2012) Laser plasma jet driven microparticles for DNA/drug delivery. PLoS ONE 7:e50823. doi:10.1371/journal.pone.0050823

    Google Scholar 

  131. Kawakami S, Higuchi Y, Hashida M (2008) Nonviral approaches for targeted delivery of plasmid DNA and oligonucleotide. J Pharm Sci 97:726–745. doi:10.1002/jps.21024

    Google Scholar 

  132. Passineau MJ, Zourelias L, Machen L et al (2010) Ultrasound-assisted non-viral gene transfer to the salivary glands. Gene Ther 17:1318–1324. doi:10.1038/gt.2010.86

    Google Scholar 

  133. Al-Dosari MS, Gao X (2009) Nonviral gene delivery: principle, limitations, and recent progress. AAPS J 11:671–681. doi:10.1208/s12248-009-9143-y

    Google Scholar 

  134. Wolff JA, Ludtke JJ, Acsadi G et al (1992) Long-term persistence of plasmid DNA and foreign gene expression in mouse muscle. Hum Mol Genet 1:363–369

    Google Scholar 

  135. Hagstrom JE, Hegge J, Zhang G et al (2004) A facile nonviral method for delivering genes and siRNAs to skeletal muscle of mammalian limbs. Mol Ther 10:386–398. doi:10.1016/j.ymthe.2004.05.004

    Google Scholar 

  136. Sebestyén MG, Hegge JO, Noble MA et al (2007) Progress toward a nonviral gene therapy protocol for the treatment of anemia. Hum Gene Ther 18:269–285. doi:10.1089/hum.2006.186

    Google Scholar 

  137. Kawabata K, Takakura Y, Hashida M (1995) The fate of plasmid DNA after intravenous injection in mice: involvement of scavenger receptors in its hepatic uptake. Pharm Res 12:825–830

    Google Scholar 

  138. Wang M, Orsini C, Casanova D et al (2001) MUSEAP, a novel reporter gene for the study of long-term gene expression in immunocompetent mice. Gene 279:99–108

    Google Scholar 

  139. Vandermeulen G, Marie C, Scherman D, Préat V (2011) New generation of plasmid backbones devoid of antibiotic resistance marker for gene therapy trials. Mol Ther 19:1942–1949. doi:10.1038/mt.2011.182

    Google Scholar 

  140. Kanwar JR, Roy K, Kanwar RK (2011) Chimeric aptamers in cancer cell-targeted drug delivery. Crit Rev Biochem Mol Biol 46:459–477. doi:10.3109/10409238.2011.614592

    Google Scholar 

  141. Bouchard PR, Hutabarat RM, Thompson KM (2010) Discovery and development of therapeutic aptamers. Annu Rev Pharmacol Toxicol 50:237–257. doi:10.1146/annurev.pharmtox.010909.105547

    Google Scholar 

  142. Huang D-B, Vu D, Cassiday LA et al (2003) Crystal structure of NF-kappaB (p50)2 complexed to a high-affinity RNA aptamer. Proc Natl Acad Sci USA 100:9268–9273. doi:10.1073/pnas.1632011100

    Google Scholar 

  143. Mashima T, Matsugami A, Nishikawa F et al (2009) Unique quadruplex structure and interaction of an RNA aptamer against bovine prion protein. Nucleic Acids Res 37:6249–6258. doi:10.1093/nar/gkp647

    Google Scholar 

  144. Phan AT, Kuryavyi V, Darnell JC et al (2011) Structure-function studies of FMRP RGG peptide recognition of an RNA duplex-quadruplex junction. Nat Struct Mol Biol 18:796–804. doi:10.1038/nsmb.2064

    Google Scholar 

  145. Sussman D, Wilson C (2000) A water channel in the core of the vitamin B(12) RNA aptamer. Structure 8:719–727

    Google Scholar 

  146. Ellington AD, Szostak JW (1990) In vitro selection of RNA molecules that bind specific ligands. Nature 346:818–822. doi:10.1038/346818a0

    Google Scholar 

  147. Ellington AD, Szostak JW (1992) Selection in vitro of single-stranded DNA molecules that fold into specific ligand-binding structures. Nature 355:850–852. doi:10.1038/355850a0

    Google Scholar 

  148. Tuerk C, Gold L (1990) Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science 249:505–510

    Google Scholar 

  149. Nutiu R, Li Y (2005) In vitro selection of structure-switching signaling aptamers. Angew Chem Int Ed Engl 44:1061–1065. doi:10.1002/anie.200461848

    Google Scholar 

  150. Stoltenburg R, Nikolaus N, Strehlitz B (2012) Capture-SELEX: selection of DNA aptamers for aminoglycoside antibiotics. J Anal Methods Chem 2012:415697. doi:10.1155/2012/415697

    Google Scholar 

  151. Binning JM, Leung DW, Amarasinghe GK (2012) Aptamers in virology: recent advances and challenges. Front Microbiol 3:29. doi:10.3389/fmicb.2012.00029

    Google Scholar 

  152. Kang D, Wang J, Zhang W et al (2012) Selection of DNA aptamers against glioblastoma cells with high affinity and specificity. PLoS ONE 7:e42731. doi:10.1371/journal.pone.0042731

    Google Scholar 

  153. Eckstein F, Gish G (1989) Phosphorothioates in molecular biology. Trends Biochem Sci 14:97–100

    Google Scholar 

  154. Green LS, Jellinek D, Bell C et al (1995) Nuclease-resistant nucleic acid ligands to vascular permeability factor/vascular endothelial growth factor. Chem Biol 2:683–695

    Google Scholar 

  155. Ruckman J, Green LS, Beeson J et al (1998) 2′-Fluoropyrimidine RNA-based aptamers to the 165-amino acid form of vascular endothelial growth factor (VEGF165). Inhibition of receptor binding and VEGF-induced vascular permeability through interactions requiring the exon 7-encoded domain. J Biol Chem 273:20556–20567

    Google Scholar 

  156. Lin Y, Nieuwlandt D, Magallanez A et al (1996) High-affinity and specific recognition of human thyroid stimulating hormone (hTSH) by in vitro-selected 2′-amino-modified RNA. Nucleic Acids Res 24:3407–3414

    Google Scholar 

  157. Keefe AD, Pai S, Ellington A (2010) Aptamers as therapeutics. Nat Rev Drug Discov 9:537–550. doi:10.1038/nrd3141

    Google Scholar 

  158. Khar RK, Jain GK, Warsi MH et al (2010) Nano-vectors for the ocular delivery of nucleic acid-based therapeutics. Indian J Pharm Sci 72:675–688. doi:10.4103/0250-474X.84575

    Google Scholar 

  159. Sanghvi YS (2011) A status update of modified oligonucleotides for chemotherapeutics applications. Curr Protoc Nucleic Acid Chem Chap 4: Unit 4.1.1–22. Doi: 10.1002/0471142700.nc0401s46

  160. Thiel KW, Giangrande PH (2009) Therapeutic applications of DNA and RNA aptamers. Oligonucleotides 19:209–222. doi:10.1089/oli.2009.0199

    Google Scholar 

  161. Cohen MG, Purdy DA, Rossi JS et al (2010) First clinical application of an actively reversible direct factor IXa inhibitor as an anticoagulation strategy in patients undergoing percutaneous coronary intervention. Circulation 122:614–622. doi:10.1161/CIRCULATIONAHA.109.927756

    Google Scholar 

  162. Altman S, Cech TR (2013) The nobel prize in chemistry 1989. http://www.nobelprize.org/nobel_prizes/chemistry/laureates/1989/. Accessed 4 Apr 2013

  163. Scherer LJ, Rossi JJ (2003) Approaches for the sequence-specific knockdown of mRNA. Nat Biotechnol 21:1457–1465. doi:10.1038/nbt915

    Google Scholar 

  164. Burke JM (1996) Hairpin ribozyme: current status and future prospects. Biochem Soc Trans 24:608–615

    Google Scholar 

  165. Usman N, Beigelman L, McSwiggen JA (1996) Hammerhead ribozyme engineering. Curr Opin Struct Biol 6:527–533

    Google Scholar 

  166. El-Sagheer AH, Brown T (2010) New strategy for the synthesis of chemically modified RNA constructs exemplified by hairpin and hammerhead ribozymes. Proc Natl Acad Sci USA 107:15329–15334. doi:10.1073/pnas.1006447107

    Google Scholar 

  167. Liang JC, Bloom RJ, Smolke CD (2011) Engineering biological systems with synthetic RNA molecules. Mol Cell 43:915–926. doi:10.1016/j.molcel.2011.08.023

    Google Scholar 

  168. Wieland M, Berschneider B, Erlacher MD, Hartig JS (2010) Aptazyme-mediated regulation of 16S ribosomal RNA. Chem Biol 17:236–242. doi:10.1016/j.chembiol.2010.02.012

    Google Scholar 

  169. Sarver N, Cantin EM, Chang PS et al (1990) Ribozymes as potential anti-HIV-1 therapeutic agents. Science 247:1222–1225

    Google Scholar 

  170. Yu M, Ojwang J, Yamada O et al (1993) A hairpin ribozyme inhibits expression of diverse strains of human immunodeficiency virus type 1. Proc Natl Acad Sci USA 90:6340–6344

    Google Scholar 

  171. Dropulić B, Lin NH, Martin MA, Jeang KT (1992) Functional characterization of a U5 ribozyme: intracellular suppression of human immunodeficiency virus type 1 expression. J Virol 66:1432–1441

    Google Scholar 

  172. Ojwang JO, Hampel A, Looney DJ et al (1992) Inhibition of human immunodeficiency virus type 1 expression by a hairpin ribozyme. Proc Natl Acad Sci USA 89:10802–10806

    Google Scholar 

  173. Wong-Staal F, Poeschla EM, Looney DJ (1998) A controlled, phase 1 clinical trial to evaluate the safety and effects in HIV-1 infected humans of autologous lymphocytes transduced with a ribozyme that cleaves HIV-1 RNA. Hum Gene Ther 9:2407–2425. doi:10.1089/hum.1998.9.16-2407

    Google Scholar 

  174. (2013) Press release: the 2006 nobel prize in physiology or medicine. http://www.nobelprize.org/nobel_prizes/medicine/laureates/2006/press.html. Accessed 12 Apr 2013

  175. Pecot CV, Calin GA, Coleman RL et al (2011) RNA interference in the clinic: challenges and future directions. Nat Rev Cancer 11:59–67. doi:10.1038/nrc2966

    Google Scholar 

  176. Sibley CR, Seow Y, Wood MJA (2010) Novel RNA-based strategies for therapeutic gene silencing. Mol Ther 18:466–476. doi:10.1038/mt.2009.306

    Google Scholar 

  177. Cho Y-S, Lee GY, Sajja HK et al (2013) Targeted delivery of siRNA-generating DNA nanocassettes using multifunctional nanoparticles. Small. doi:10.1002/smll.201201973

    Google Scholar 

  178. Wall NR, Shi Y (2003) Small RNA: can RNA interference be exploited for therapy? Lancet 362:1401–1403. doi:10.1016/S0140-6736(03)14637-5

    Google Scholar 

  179. Dalby B, Cates S, Harris A et al (2004) Advanced transfection with Lipofectamine 2000 reagent: primary neurons, siRNA, and high-throughput applications. Methods 33:95–103. doi:10.1016/j.ymeth.2003.11.023

    Google Scholar 

  180. McCaffrey AP, Meuse L, Pham T-TT et al (2002) RNA interference in adult mice. Nature 418:38–39. doi:10.1038/418038a

    Google Scholar 

  181. Liu YP, Vink MA, Westerink J-T et al (2010) Titers of lentiviral vectors encoding shRNAs and miRNAs are reduced by different mechanisms that require distinct repair strategies. RNA 16:1328–1339. doi:10.1261/rna.1887910

    Google Scholar 

  182. Van den Haute C, Eggermont K, Nuttin B et al (2003) Lentiviral vector-mediated delivery of short hairpin RNA results in persistent knockdown of gene expression in mouse brain. Hum Gene Ther 14:1799–1807. doi:10.1089/104303403322611809

    Google Scholar 

  183. Halder J, Kamat AA, Landen CN Jr et al (2006) Focal adhesion kinase targeting using in vivo short interfering RNA delivery in neutral liposomes for ovarian carcinoma therapy. Clin Cancer Res 12:4916–4924. doi:10.1158/1078-0432.CCR-06-0021

    Google Scholar 

  184. Sato Y, Murase K, Kato J et al (2008) Resolution of liver cirrhosis using vitamin A-coupled liposomes to deliver siRNA against a collagen-specific chaperone. Nat Biotechnol 26:431–442. doi:10.1038/nbt1396

    Google Scholar 

  185. Frank-Kamenetsky M, Grefhorst A, Anderson NN et al (2008) Therapeutic RNAi targeting PCSK9 acutely lowers plasma cholesterol in rodents and LDL cholesterol in nonhuman primates. Proc Natl Acad Sci USA 105:11915–11920. doi:10.1073/pnas.0805434105

    Google Scholar 

  186. Marquez VE, Siddiqui MA, Ezzitouni A et al (1996) Nucleosides with a twist. Can fixed forms of sugar ring pucker influence biological activity in nucleosides and oligonucleotides? J Med Chem 39:3739–3747. doi:10.1021/jm960306+

    Google Scholar 

  187. Deleavey GF, Damha MJ (2012) Designing chemically modified oligonucleotides for targeted gene silencing. Chem Biol 19:937–954. doi:10.1016/j.chembiol.2012.07.011

    Google Scholar 

  188. McNeer NA, Schleifman EB, Cuthbert A et al (2012) Systemic delivery of triplex-forming PNA and donor DNA by nanoparticles mediates site-specific genome editing of human hematopoietic cells in vivo. Gene Ther. doi:10.1038/gt.2012.82

    Google Scholar 

  189. Rogers FA, Hu R-H, Milstone LM (2013) Local delivery of gene-modifying triplex-forming molecules to the epidermis. J Invest Dermatol 133:685–691. doi:10.1038/jid.2012.351

    Google Scholar 

  190. Chakrabarti A, Zhang K, Aruva MR et al (2007) Radiohybridization PET imaging of KRAS G12D mRNA expression in human pancreas cancer xenografts with [(64)Cu]DO3A-peptide nucleic acid-peptide nanoparticles. Cancer Biol Ther 6:948–956

    Google Scholar 

  191. 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. doi:10.1007/s00253-006-0434-2

    Google Scholar 

  192. Campbell MA, Wengel J (2011) Locked vs. unlocked nucleic acids (LNA vs. UNA): contrasting structures work towards common therapeutic goals. Chem Soc Rev 40:5680–5689. doi:10.1039/c1cs15048k

    Google Scholar 

  193. Li Y-F, Morcos PA (2008) Design and synthesis of dendritic molecular transporter that achieves efficient in vivo delivery of morpholino antisense oligo. Bioconjug Chem 19:1464–1470. doi:10.1021/bc8001437

    Google Scholar 

  194. Eisen JS, Smith JC (2008) Controlling morpholino experiments: don’t stop making antisense. Development 135:1735–1743. doi:10.1242/dev.001115

    Google Scholar 

  195. Huh D, Hamilton GA, Ingber DE (2011) From 3D cell culture to organs-on-chips. Trends Cell Biol 21:745–754. doi:10.1016/j.tcb.2011.09.005

    Google Scholar 

  196. Kelkar SS, Reineke TM (2011) Theranostics: combining imaging and therapy. Bioconjug Chem 22:1879–1903. doi:10.1021/bc200151q

    Google Scholar 

Download references

Acknowledgments

The authors are indebted to Drs. William Heetderks and Antonio Sastre for their critical review and to Ms. Christine Rogers for her assistance with preparing the manuscript. Figure 26.4 Used with permission and modified from Biochimica et Biophysica Acta (BBA)—Proteins and Proteomics, 1697, Yoon S. Cho-Chung, Antisense protein kinase A RIα-induced tumor reversion: portrait of a microarray, 71–79, Copyright 2004, with permission from Elsevier.

Conflict of Interest

The authors declare that they have no conflict of interests.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Belinda Seto .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer-Verlag London

About this chapter

Cite this chapter

Conroy, R., Seto, B. (2014). Multifunctional Nanoscale Delivery Systems for Nucleic Acids. In: Cai, W. (eds) Engineering in Translational Medicine. Springer, London. https://doi.org/10.1007/978-1-4471-4372-7_18

Download citation

  • DOI: https://doi.org/10.1007/978-1-4471-4372-7_18

  • Published:

  • Publisher Name: Springer, London

  • Print ISBN: 978-1-4471-4371-0

  • Online ISBN: 978-1-4471-4372-7

  • eBook Packages: EngineeringEngineering (R0)

Publish with us

Policies and ethics