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Molecular Engineering to Enhance Aptamer Functionality

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Aptamers Selected by Cell-SELEX for Theranostics

Abstract

Rapid development of bioanalysis and biomedicine requires enhanced and multiple functionality of aptamers. The field of molecular engineering has advanced to a stage where more and more molecular functions can be rationally designed in a predictable manner. By combining these two fields together, aptamer-based molecular engineering is able to tune the functionalities of aptamers toward more complicated and effective biological and biomedical applications. In this chapter, we focus on introducing the substantial progress in the development of using smart ways to broaden the multifunctional and logical applications of aptamers.

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References

  1. Liu J, Cao Z, Lu Y (2009) Functional nucleic acid sensors. Chem Rev 109(5):1948–1998

    Article  CAS  Google Scholar 

  2. Xing H et al (2012) DNA aptamer functionalized nanomaterials for intracellular analysis, cancer cell imaging and drug delivery. Curr Opin Chem Biol 16(3–4):429–435

    Article  CAS  Google Scholar 

  3. Seferos DS et al (2007) Nano-flares: probes for transfection and mRNA detection in living cells. J Am Chem Soc 129(50):15477–15479

    Article  CAS  Google Scholar 

  4. Zheng D et al (2009) Aptamer nano-flares for molecular detection in living cells. Nano Lett 9(9):3258–3261

    Article  CAS  Google Scholar 

  5. Rosi NL et al (2006) Oligonucleotide-modified gold nanoparticles for intracellular gene regulation. Science 312(5776):1027–1030

    Article  CAS  Google Scholar 

  6. Jayagopal A et al (2010) Hairpin DNA-functionalized gold colloids for the imaging of mRNA in live cells. J Am Chem Soc 132(28):9789–9796

    Article  CAS  Google Scholar 

  7. Wang Y et al (2010) Aptamer/graphene oxide nanocomplex for in situ molecular probing in living cells. J Am Chem Soc 132(27):9274–9276

    Article  CAS  Google Scholar 

  8. Li Y et al (2004) Controlled assembly of dendrimer-like DNA. Nat Mater 3(1):38–42

    Article  CAS  Google Scholar 

  9. Goodman RP et al (2005) Rapid chiral assembly of rigid DNA building blocks for molecular nanofabrication. Science 310(5754):1661–1665

    Article  CAS  Google Scholar 

  10. Aldaye FA, Palmer AL, Sleiman HF (2008) Assembling materials with DNA as the guide. Science 321(5897):1795–1799

    Article  CAS  Google Scholar 

  11. Yin P et al (2008) Programming DNA tube circumferences. Science 321(5890):824–826

    Article  CAS  Google Scholar 

  12. Afonin KA et al (2010) In vitro assembly of cubic RNA-based scaffolds designed in silico. Nat Nano 5(9):676–682

    Article  CAS  Google Scholar 

  13. Gu H et al (2010) A proximity-based programmable DNA nanoscale assembly line. Nature 465(7295):202–205

    Article  CAS  Google Scholar 

  14. Severcan I et al (2010) A polyhedron made of tRNAs. Nat Chem 2(9):772–779

    Article  CAS  Google Scholar 

  15. Wu C et al (2013) Building a multifunctional aptamer-based DNA nanoassembly for targeted cancer therapy. J Am Chem Soc 135(49):18644–18650

    Article  CAS  Google Scholar 

  16. Zhu GZ et al (2013) Noncanonical self-assembly of multifunctional DNA nanoflowers for biomedical applications. J Am Chem Soc 135(44):16438–16445

    Article  CAS  Google Scholar 

  17. Lee YC, Lee RT (1995) Carbohydrate-protein interactions: basis of glycobiology. Acc Chem Res 28(8):321–327

    Article  CAS  Google Scholar 

  18. Mammen M, Choi S-K, Whitesides GM (1998) Polyvalent interactions in biological systems: implications for design and use of multivalent ligands and inhibitors. Angew Chem Int Ed 37(20):2754–2794

    Article  Google Scholar 

  19. Kortt AA et al (2001) Dimeric and trimeric antibodies: high avidity scFvs for cancer targeting. Biomol Eng 18(3):95–108

    Article  CAS  Google Scholar 

  20. Rusconi CP et al (2002) RNA aptamers as reversible antagonists of coagulation factor IXa. Nature 419(6902):90–94

    Article  CAS  Google Scholar 

  21. Kim Y, Cao Z, Tan W (2008) Molecular assembly for high-performance bivalent nucleic acid inhibitor. Proc Natl Acad Sci 105(15):5664–5669

    Article  CAS  Google Scholar 

  22. Hirsh J (2003) Current anticoagulant therapy—unmet clinical needs. Thromb Res 109:S1–S8

    Google Scholar 

  23. Tasset DM, Kubik MF, Steiner W (1997) Oligonucleotide inhibitors of human thrombin that bind distinct epitopes. J Mol Biol 272(5):688–698

    Article  CAS  Google Scholar 

  24. Deng B et al (2014) Aptamer binding assays for proteins: the thrombin example—a review. Anal Chim Acta 837:1–15

    Article  CAS  Google Scholar 

  25. Nimjee SM et al (2005) The potential of aptamers as anticoagulants. Trends Cardiovasc Med 15(1):41–45

    Article  CAS  Google Scholar 

  26. Wang K et al (2009) Molecular engineering of DNA: molecular beacons. Angew Chem Int Ed 48(5):856–870

    Article  CAS  Google Scholar 

  27. Tyagi S, Kramer FR (1996) Molecular beacons: probes that fluoresce upon hybridization. Nat Biotech 14(3):303–308

    Article  CAS  Google Scholar 

  28. Wang L et al (2005) Locked nucleic acid molecular beacons. J Am Chem Soc 127(45):15664–15665

    Article  CAS  Google Scholar 

  29. Yang CJ et al (2006) Hybrid molecular probe for nucleic acid analysis in biological samples. J Am Chem Soc 128(31):9986–9987

    Article  CAS  Google Scholar 

  30. Wu Y et al (2008) Nucleic acid beacons for long-term real-time intracellular monitoring. Anal Chem 80(8):3025–3028

    Article  CAS  Google Scholar 

  31. Tyagi S (2009) Imaging intracellular RNA distribution and dynamics in living cells. Nat Meth 6(5):331–338

    Article  CAS  Google Scholar 

  32. Sharifi S et al (2012) Toxicity of nanomaterials. Chem Soc Rev 41(6):2323–2343

    Article  CAS  Google Scholar 

  33. Liu H et al (2010) DNA-based micelles: synthesis, micellar properties and size-dependent cell permeability. Chem Eur J 16(12):3791–3797

    Article  CAS  Google Scholar 

  34. Wu Y et al (2010) DNA aptamer–micelle as an efficient detection/delivery vehicle toward cancer cells. Proc Natl Acad Sci 107(1):5–10

    Article  CAS  Google Scholar 

  35. Chen T et al (2013) DNA micelle flares for intracellular mRNA imaging and gene therapy. Angew Chem Int Ed 52(7):2012–2016

    Article  CAS  Google Scholar 

  36. Wu C et al (2013) Engineering of switchable aptamer micelle flares for molecular imaging in living cells. ACS Nano 7(7):5724–5731

    Article  CAS  Google Scholar 

  37. Tang Z et al (2008) Aptamer switch probe based on intramolecular displacement. J Am Chem Soc 130(34):11268–11269

    Article  CAS  Google Scholar 

  38. Lin CH, Patei DJ (1997) Structural basis of DNA folding and recognition in an AMP-DNA aptamer complex: distinct architectures but common recognition motifs for DNA and RNA aptamers complexed to AMP. Chem Biol 4(11):817–832

    Article  CAS  Google Scholar 

  39. Nutiu R, Li Y (2003) Structure-switching signaling aptamers. J Am Chem Soc 125(16):4771–4778

    Article  CAS  Google Scholar 

  40. Li N, Ho C-M (2008) Aptamer-based optical probes with separated molecular recognition and signal transduction modules. J Am Chem Soc 130(8):2380–2381

    Article  CAS  Google Scholar 

  41. Bonnet G, Krichevsky O, Libchaber A (1998) Kinetics of conformational fluctuations in DNA hairpin-loops. Proc Natl Acad Sci 95(15):8602–8606

    Article  CAS  Google Scholar 

  42. Wang J et al (2012) Assembly of aptamer switch probes and photosensitizer on gold nanorods for targeted photothermal and photodynamic cancer therapy. ACS Nano 6(6):5070–5077

    Article  CAS  Google Scholar 

  43. Zheng G et al (2007) Photodynamic molecular beacon as an activatable photosensitizer based on protease-controlled singlet oxygen quenching and activation. Proc Natl Acad Sci USA 104(21):8989–8994

    Article  CAS  Google Scholar 

  44. McDonnell SO et al (2005) Supramolecular photonic therapeutic agents. J Am Chem Soc 127(47):16360–16361

    Article  CAS  Google Scholar 

  45. Zhu Z et al (2008) Regulation of singlet oxygen generation using single-walled carbon nanotubes. J Am Chem Soc 130(33):10856–10857

    Article  CAS  Google Scholar 

  46. Tang ZW et al (2010) Aptamer-target binding triggered molecular mediation of singlet oxygen generation. Chem Asian J 5(4):783–786

    Article  CAS  Google Scholar 

  47. Wang KL et al (2011) Self-assembly of a bifunctional DNA carrier for drug delivery. Ange Chem Int Ed 50(27):6098–6101

    Article  CAS  Google Scholar 

  48. Ball P (2000) Chemistry meets computing. Nature 406(6792):118–120

    Article  CAS  Google Scholar 

  49. Goldman N et al (2013) Towards practical, high-capacity, low-maintenance information storage in synthesized DNA. Nature 494(7435):77–80

    Article  CAS  Google Scholar 

  50. Church GM, Gao Y, Kosuri S (2012) Next-generation digital information storage in DNA. Science 337(6102):1628

    Article  CAS  Google Scholar 

  51. Adleman LM (1994) Molecular computation of solutions to combinatorial problems. Science 266(5187):1021–1024

    Article  CAS  Google Scholar 

  52. Vuyisich M, Beal PA (2002) Controlling protein activity with ligand-regulated RNA aptamers. Chem Biol 9(8):907–913

    Article  CAS  Google Scholar 

  53. Lee JF, Stovall GM, Ellington AD (2006) Aptamer therapeutics advance. Curr Opin Chem Biol 10(3):282–289

    Article  CAS  Google Scholar 

  54. Kolpashchikov DM, Stojanovic MN (2005) Boolean control of aptamer binding states. J Am Chem Soc 127(32):11348–11351

    Article  CAS  Google Scholar 

  55. Zhou M et al (2010) Aptamer-controlled biofuel cells in logic systems and used as self-powered and intelligent logic aptasensors. J Am Chem Soc 132(7):2172–2174

    Article  CAS  Google Scholar 

  56. Han D et al (2012) A logical molecular circuit for programmable and autonomous regulation of protein activity using DNA aptamer-protein interactions. J Am Chem Soc 134(51):20797–20804

    Article  CAS  Google Scholar 

  57. Han D et al (2013) Engineering a cell-surface aptamer circuit for targeted and amplified photodynamic cancer therapy. ACS Nano 7(3):2312–2319

    Article  CAS  Google Scholar 

  58. You MX et al (2014) DNA “nano-claw”: logic-based autonomous cancer targeting and therapy. J Am Chem Soc 136(4):1256–1259

    Article  CAS  Google Scholar 

  59. Nutiu R, Li YF (2003) Structure-switching signaling aptamers. J Am Chem Soc 125(16):4771–4778

    Article  CAS  Google Scholar 

  60. Douglas SM, Bachelet I, Church GM (2012) A logic-gated nanorobot for targeted transport of molecular payloads. Science 335(6070):831–834

    Article  CAS  Google Scholar 

  61. Rothemund PWK (2006) Folding DNA to create nanoscale shapes and patterns. Nature 440(7082):297–302

    Article  CAS  Google Scholar 

  62. Rudchenko M et al (2013) Autonomous molecular cascades for evaluation of cell surfaces. Nat Nanotechnol 8(8):580–586

    Article  CAS  Google Scholar 

  63. Zhang DY, Winfree E (2009) Control of DNA strand displacement kinetics using toehold exchange. J Am Chem Soc 131(47):17303–17314

    Article  CAS  Google Scholar 

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Correspondence to Da Han .

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Han, D., Wu, C., Tan, W. (2015). Molecular Engineering to Enhance Aptamer Functionality. In: Tan, W., Fang, X. (eds) Aptamers Selected by Cell-SELEX for Theranostics. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-46226-3_5

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