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RNA Nanotechnology Approach for Targeted Delivery of RNA Therapeutics Using Cell-Internalizing Aptamers

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DNA and RNA Nanobiotechnologies in Medicine: Diagnosis and Treatment of Diseases

Part of the book series: RNA Technologies ((RNATECHN))

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Abstract

The development of RNA-based therapeutics has progressed rapidly in recent years. RNA aptamers are a form of nanoparticles ranging in size from 10 to 50 nm, which is optimal for effective systemic delivery to diseased tissues. This review mainly focuses on the recent developments in the evolution and use of aptamers as therapeutic agents. As part of this review, we explore two major aptamer selection processes using both purified ligands and whole cell-based selection methods. Particular attention will be given to the concept of evolving aptamers that bind to cell surface receptors, which are internalized upon ligand binding. Aptamers can be conjugated with other cytotoxic RNA therapeutics to form a chimera through RNA nanotechnology. Examples of various aptamer-mediated delivery strategies will be discussed. It has become apparent that innovative aptamer-based nanomedicines will soon prove to be important and become a more widely used therapeutic modality for the treatment of disease. We will discuss the advantages and also the challenges of developing aptamers as therapeutic agents and as vehicles for siRNA delivery.

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References

  • Anilkumar G, Rajasekaran SA, Wang S et al (2003) Prostate-specific membrane antigen association with filamin A modulates its internalization and NAALADase activity. Cancer Res 63:2645–2648

    PubMed  CAS  Google Scholar 

  • Ansari AZ (2007) Chemical crosshairs on the central dogma. Nat Chem Biol 3:2–7

    Article  PubMed  CAS  Google Scholar 

  • Arteaga CL, Sliwkowski MX, Osborne CK et al (2012) Treatment of HER2-positive breast cancer: current status and future perspectives. Nat Rev Clin Oncol 9:16–32

    Article  CAS  Google Scholar 

  • Bagalkot V, Farokhzad OC, Langer R et al (2006) An aptamer-doxorubicin physical conjugate as a novel targeted drug-delivery platform. Angew Chem Int Ed Engl 45:8149–8152

    Article  PubMed  CAS  Google Scholar 

  • Bauman J, Jearawiriyapaisarn N, Kole R (2009) Therapeutic potential of splice-switching oligonucleotides. Oligonucleotides 19:1–13

    Article  PubMed  CAS  Google Scholar 

  • Bunka DH, Stockley PG (2006) Aptamers come of age - at last. Nat Rev Microbiol 4:588–596

    Article  PubMed  CAS  Google Scholar 

  • Burnett JC, Rossi JJ (2012) RNA-based therapeutics: current progress and future prospects. Chem Biol 19:60–71

    Article  PubMed  CAS  Google Scholar 

  • Cao Z, Tong R, Mishra A et al (2009) Reversible cell-specific drug delivery with aptamer-functionalized liposomes. Angew Chem Int Ed Engl 48:6494–6498

    Article  PubMed  CAS  Google Scholar 

  • Caruthers MH (2012) The chemical synthesis of DNA/RNA – our gift to science. J Biol Chem 288(2):1420–1427

    Article  PubMed  CAS  Google Scholar 

  • Castanotto D, Rossi JJ (2009) The promises and pitfalls of RNA-interference-based therapeutics. Nature 457:426–433

    Article  PubMed  CAS  Google Scholar 

  • Chen CH, Dellamaggiore KR, Ouellette CP et al (2008) Aptamer-based endocytosis of a lysosomal enzyme. Proc Natl Acad Sci USA 105:15908–15913

    Article  PubMed  CAS  Google Scholar 

  • Chu TC, Marks JW 3rd, Lavery LA et al (2006a) Aptamer:toxin conjugates that specifically target prostate tumor cells. Cancer Res 66:5989–5992

    Article  PubMed  CAS  Google Scholar 

  • Chu TC, Twu KY, Ellington AD et al (2006b) Aptamer mediated siRNA delivery. Nucleic Acids Res 34:e73

    Article  PubMed  CAS  Google Scholar 

  • Dassie JP, Liu XY, Thomas GS et al (2009) Systemic administration of optimized aptamer-siRNA chimeras promotes regression of PSMA-expressing tumors. Nat Biotechnol 27:839–849

    Article  PubMed  CAS  Google Scholar 

  • Devincenzo JP (2012) The promise, pitfalls and progress of RNA-interference-based antiviral therapy for respiratory viruses. Antivir Ther 17:213–225

    Article  PubMed  CAS  Google Scholar 

  • Dhar S, Gu FX, Langer R et al (2008) Targeted delivery of cisplatin to prostate cancer cells by aptamer functionalized Pt(IV) prodrug-PLGA-PEG nanoparticles. Proc Natl Acad Sci USA 105:17356–17361

    Article  PubMed  CAS  Google Scholar 

  • Dominska M, Dykxhoorn DM (2010) Breaking down the barriers: siRNA delivery and endosome escape. J Cell Sci 123:1183–1189

    Article  PubMed  CAS  Google Scholar 

  • Doria M (2011) Role of the CD4 down-modulation activity of Nef in HIV-1 infectivity. Curr HIV Res 9:490–495

    Article  PubMed  CAS  Google Scholar 

  • Dua P, Kim S, Lee DK (2011) Nucleic acid aptamers targeting cell-surface proteins. Methods 54:215–225

    Article  PubMed  CAS  Google Scholar 

  • Ellington AD, Szostak JW (1990) In vitro selection of RNA molecules that bind specific ligands. Nature 346:818–822

    Article  PubMed  CAS  Google Scholar 

  • Farokhzad OC, Cheng J, Teply BA et al (2006) Targeted nanoparticle-aptamer bioconjugates for cancer chemotherapy in vivo. Proc Natl Acad Sci USA 103:6315–6320

    Article  PubMed  CAS  Google Scholar 

  • Ferreira CS, Cheung MC, Missailidis S et al (2009) Phototoxic aptamers selectively enter and kill epithelial cancer cells. Nucleic Acids Res 37:866–876

    Article  PubMed  CAS  Google Scholar 

  • Ghosh A, Heston WD (2004) Tumor target prostate specific membrane antigen (PSMA) and its regulation in prostate cancer. J Cell Biochem 91:528–539

    Article  PubMed  CAS  Google Scholar 

  • Gopinath SC (2007) Methods developed for SELEX. Anal Bioanal Chem 387:171–182

    Article  PubMed  CAS  Google Scholar 

  • Govindarajan S, Goldstein RA (1998) On the thermodynamic hypothesis of protein folding. Proc Natl Acad Sci USA 95:5545–5549

    Article  PubMed  CAS  Google Scholar 

  • Gunther M, Lipka J, Malek A et al (2011) Polyethylenimines for RNAi-mediated gene targeting in vivo and siRNA delivery to the lung. Eur J Pharm Biopharm 77:438–449

    Article  PubMed  CAS  Google Scholar 

  • Guo P (2002) Structure and function of phi29 hexameric RNA that drives the viral DNA packaging motor: review. Prog Nucleic Acid Res Mol Biol 72:415–472

    Article  PubMed  CAS  Google Scholar 

  • Guo P (2005) RNA nanotechnology: engineering, assembly and applications in detection, gene delivery and therapy. J Nanosci Nanotechnol 5:1964–1982

    Article  PubMed  CAS  Google Scholar 

  • Guo P (2010) The emerging field of RNA nanotechnology. Nat Nanotechnol 5:833–842

    Article  PubMed  CAS  Google Scholar 

  • Guo P (2011) RNA Nanotechnology: methods for synthesis, conjugation, assembly and application of RNA nanoparticles. Methods 54:201–203

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Guo KT, Paul A, Schichor C et al (2008a) CELL-SELEX: novel perspectives of aptamer-based therapeutics. Int J Mol Sci 9:668–678

    Article  PubMed  CAS  Google Scholar 

  • Guo P, Coban O, Snead NM et al (2010) Engineering RNA for targeted siRNA delivery and medical application. Adv Drug Deliv Rev 62:650–666

    Article  PubMed  CAS  Google Scholar 

  • Guo P, Haque F, Hallahan B et al (2012a) Uniqueness, advantages, challenges, solutions, and perspectives in therapeutics applying RNA nanotechnology. Nucleic Acid Ther 22:226–245

    PubMed  CAS  Google Scholar 

  • Guo P, Shu Y, Binzel D et al (2012b) Synthesis, conjugation, and labeling of multifunctional pRNA nanoparticles for specific delivery of siRNA, drugs, and other therapeutics to target cells. Methods Mol Biol 928:197–219

    PubMed  CAS  Google Scholar 

  • Haasnoot J, Berkhout B (2009) Nucleic acids-based therapeutics in the battle against pathogenic viruses. Handb Exp Pharmacol 189:243–263

    Article  PubMed  CAS  Google Scholar 

  • Haque F, Shu D, Shu Y et al (2012) Ultrastable synergistic tetravalent RNA nanoparticles for targeting to cancers. Nano Today 7:245–257

    Article  PubMed  CAS  Google Scholar 

  • Heng X, Kharytonchyk S, Garcia EL et al (2012) Identification of a minimal region of the HIV-1 5′-leader required for RNA dimerization, NC binding, and packaging. J Mol Biol 417:224–239

    Article  PubMed  CAS  Google Scholar 

  • Hicke BJ, Stephens AW (2000) Escort aptamers: a delivery service for diagnosis and therapy. J Clin Invest 106:923–928

    Article  PubMed  CAS  Google Scholar 

  • Ho SP, Britton DH, Stone BA et al (1996) Potent antisense oligonucleotides to the human multidrug resistance-1 mRNA are rationally selected by mapping RNA-accessible sites with oligonucleotide libraries. Nucleic Acids Res 24:1901–1907

    Article  PubMed  CAS  Google Scholar 

  • Jia P, Shi T, Cai Y et al (2006) Demonstration of two novel methods for predicting functional siRNA efficiency. BMC Bioinformatics 7:271

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Kaur G, Roy I (2008) Therapeutic applications of aptamers. Expert Opin Investig Drugs 17:43–60

    Article  PubMed  CAS  Google Scholar 

  • Keefe AD, Cload ST (2008) SELEX with modified nucleotides. Curr Opin Chem Biol 12:448–456

    Article  PubMed  CAS  Google Scholar 

  • Keefe AD, Schaub RG (2008) Aptamers as candidate therapeutics for cardiovascular indications. Curr Opin Pharmacol 8:147–152

    Article  PubMed  CAS  Google Scholar 

  • Keefe A, Pai S, Ellington A (2010) Aptamers as therapeutics. Nat Rev Drug Discov 9:537–550

    Article  PubMed  CAS  Google Scholar 

  • Kim DH, Behlke MA, Rose SD et al (2005) Synthetic dsRNA dicer substrates enhance RNAi potency and efficacy. Nat Biotechnol 23:222–226

    Article  PubMed  CAS  Google Scholar 

  • Klussmann S (2006) The aptamer handbook: functional oligonucleotides and their applications. Wiley, Germany

    Book  Google Scholar 

  • Kotula JW, Pratico ED, Ming X et al (2012) Aptamer-mediated delivery of splice-switching oligonucleotides to the nuclei of cancer cells. Nucleic Acid Ther 22:187–195

    PubMed  CAS  Google Scholar 

  • Kulbachinskiy AV (2007) Methods for selection of aptamers to protein targets. Biochemistry (Mosc) 72:1505–1518

    Article  CAS  Google Scholar 

  • Kumari S, Mg S, Mayor S (2010) Endocytosis unplugged: multiple ways to enter the cell. Cell Res 20:256–275

    Article  PubMed  CAS  Google Scholar 

  • Lauridsen LH, Rothnagel JA, Veedu RN (2012) Enzymatic recognition of 2′-modified ribonucleoside 5′-triphosphates: towards the evolution of versatile aptamers. Chembiochem 13:19–25

    Article  PubMed  CAS  Google Scholar 

  • Lee JH, Canny MD, De Erkenez A et al (2005) A therapeutic aptamer inhibits angiogenesis by specifically targeting the heparin binding domain of VEGF165. Proc Natl Acad Sci USA 102:18902–18907

    Article  PubMed  CAS  Google Scholar 

  • Li W, Cha L (2007) Predicting siRNA efficiency. Cell Mol Life Sci 64:1785–1792

    Article  PubMed  CAS  Google Scholar 

  • Li L, Liu J, Diao Z et al (2009) Evaluation of specific delivery of chimeric phi29 pRNA/siRNA nanoparticles to multiple tumor cells. Mol Biosyst 5:1361–1368

    Article  PubMed  CAS  Google Scholar 

  • Liu W, Bulgaru A, Haigentz M et al (2003) The BCL2-family of protein ligands as cancer drugs: the next generation of therapeutics. Curr Med Chem Anticancer Agents 3:217–223

    Article  PubMed  CAS  Google Scholar 

  • Liu H, Guo S, Roll R et al (2007) Phi29 pRNA vector for efficient escort of hammerhead ribozyme targeting survivin in multiple cancer cells. Cancer Biol Ther 6:697–704

    Article  PubMed  CAS  Google Scholar 

  • Lupold SE, Hicke BJ, Lin Y et al (2002) Identification and characterization of nuclease-stabilized RNA molecules that bind human prostate cancer cells via the prostate-specific membrane antigen. Cancer Res 62:4029–4033

    PubMed  CAS  Google Scholar 

  • Majumder P, Gomes KN, Ulrich H (2009) Aptamers: from bench side research towards patented molecules with therapeutic applications. Expert Opin Ther Pat 19:1603–1613

    Article  PubMed  CAS  Google Scholar 

  • Markovic I, Clouse KA (2004) Recent advances in understanding the molecular mechanisms of HIV-1 entry and fusion: revisiting current targets and considering new options for therapeutic intervention. Curr HIV Res 2:223–234

    Article  PubMed  CAS  Google Scholar 

  • Mat-Arip Y, Garver K, Chen C et al (2001) Three-dimensional interaction of Phi29 pRNA dimer probed by chemical modification interference, cryo-AFM, and cross-linking. J Biol Chem 276:32575–32584

    Article  PubMed  CAS  Google Scholar 

  • Mcnamara JO 2nd, Andrechek ER, Wang Y et al (2006) Cell type-specific delivery of siRNAs with aptamer-siRNA chimeras. Nat Biotechnol 24:1005–1015

    Article  PubMed  CAS  Google Scholar 

  • Mohr SE, Perrimon N (2012) RNAi screening: new approaches, understandings, and organisms. Wiley Interdiscip Rev RNA 3:145–158

    Article  PubMed  CAS  Google Scholar 

  • Mukherjee S, Ghosh RN, Maxfield FR (1997) Endocytosis. Physiol Rev 77:759–803

    PubMed  CAS  Google Scholar 

  • Ng EW, Shima DT, Calias P et al (2006) Pegaptanib, a targeted anti-VEGF aptamer for ocular vascular disease. Nat Rev Drug Discov 5:123–132

    Article  PubMed  CAS  Google Scholar 

  • Nguyen J, Szoka FC (2012) Nucleic acid delivery: the missing pieces of the puzzle? Acc Chem Res 45:1153–1162

    Article  PubMed  CAS  Google Scholar 

  • Nimjee SM, Rusconi CP, Sullenger BA (2005) Aptamers: an emerging class of therapeutics. Annu Rev Med 56:555–583

    Article  PubMed  CAS  Google Scholar 

  • Oney S, Lam RT, Bompiani KM et al (2009) Development of universal antidotes to control aptamer activity. Nat Med 15:1224–1228

    Article  PubMed  CAS  Google Scholar 

  • Padilla R, Sousa R (2002) A Y639F/H784A T7 RNA polymerase double mutant displays superior properties for synthesizing RNAs with non-canonical NTPs. Nucleic Acids Res 30:e138

    Article  PubMed  Google Scholar 

  • Pendergrast PS, Marsh HN, Grate D et al (2005) Nucleic acid aptamers for target validation and therapeutic applications. J Biomol Tech 16:224–234

    PubMed  Google Scholar 

  • Robbins M, Judge A, Liang L et al (2007) 2′-O-methyl-modified RNAs act as TLR7 antagonists. Mol Ther 15:1663–1669

    Article  PubMed  CAS  Google Scholar 

  • Rossi JJ (2011) RNA nanoparticles come of age. Acta Biochim Biophys Sin (Shanghai) 43:245–247

    Article  Google Scholar 

  • Rusconi CP, Roberts JD, Pitoc GA et al (2004) Antidote-mediated control of an anticoagulant aptamer in vivo. Nat Biotechnol 22:1423–1428

    Article  PubMed  CAS  Google Scholar 

  • Sakurai Y, Hatakeyama H, Sato Y et al (2011) Endosomal escape and the knockdown efficiency of liposomal-siRNA by the fusogenic peptide shGALA. Biomaterials 32:5733–5742

    Article  PubMed  CAS  Google Scholar 

  • Schafer J, Hobel S, Bakowsky U et al (2010) Liposome-polyethylenimine complexes for enhanced DNA and siRNA delivery. Biomaterials 31:6892–6900

    Article  PubMed  CAS  Google Scholar 

  • Schroeder A, Levins CG, Cortez C et al (2010) Lipid-based nanotherapeutics for siRNA delivery. J Intern Med 267:9–21

    Article  PubMed  CAS  Google Scholar 

  • Sela M, White FH Jr, Anfinsen CB (1957) Reductive cleavage of disulfide bridges in ribonuclease. Science 125:691–692

    Article  PubMed  CAS  Google Scholar 

  • Shieh YA, Yang SJ, Wei MF et al (2010) Aptamer-based tumor-targeted drug delivery for photodynamic therapy. ACS Nano 4:1433–1442

    Article  PubMed  CAS  Google Scholar 

  • Shu D, Shu Y, Haque F et al (2011a) Thermodynamically stable RNA three-way junction for constructing multifunctional nanoparticles for delivery of therapeutics. Nat Nanotechnol 6:658–667

    Article  PubMed  CAS  Google Scholar 

  • Shu Y, Cinier M, Fox SR et al (2011b) Assembly of therapeutic pRNA-siRNA nanoparticles using bipartite approach. Mol Ther 19:1304–1311

    Article  PubMed  CAS  Google Scholar 

  • Shu Y, Cinier M, Shu D et al (2011c) Assembly of multifunctional phi29 pRNA nanoparticles for specific delivery of siRNA and other therapeutics to targeted cells. Methods 54:204–214

    Article  PubMed  CAS  Google Scholar 

  • Shukla GC, Haque F, Tor Y et al (2011) A boost for the emerging field of RNA nanotechnology. ACS Nano 5:3405–3418

    Article  PubMed  CAS  Google Scholar 

  • Soifer HS, Rossi JJ, Saetrom P (2007) MicroRNAs in disease and potential therapeutic applications. Mol Ther 15:2070–2079

    Article  PubMed  CAS  Google Scholar 

  • Song E, Zhu P, Lee SK et al (2005) Antibody mediated in vivo delivery of small interfering RNAs via cell-surface receptors. Nat Biotechnol 23:709–717

    Article  PubMed  CAS  Google Scholar 

  • Soundararajan S, Chen W, Spicer EK et al (2008) The nucleolin targeting aptamer AS1411 destabilizes Bcl-2 messenger RNA in human breast cancer cells. Cancer Res 68:2358–2365

    Article  PubMed  CAS  Google Scholar 

  • Soundararajan S, Wang L, Sridharan V et al (2009) Plasma membrane nucleolin is a receptor for the anticancer aptamer AS1411 in MV4-11 leukemia cells. Mol Pharmacol 76:984–991

    Article  PubMed  CAS  Google Scholar 

  • Sun W, Du L, Li M (2011) Advances and perspectives in cell-specific aptamers. Curr Pharm Des 17:80–91

    Article  PubMed  CAS  Google Scholar 

  • Talanian RV, Mcknight CJ, Rutkowski R et al (1992) Minimum length of a sequence-specific DNA binding peptide. Biochemistry 31:6871–6875

    Article  PubMed  CAS  Google Scholar 

  • Tanner JA, Shum KT (2010) Chemical biology. Kirk-Othmer encyclopedia of chemical technology, 5th edn. Wiley, New York, NY

    Google Scholar 

  • Tarapore P, Shu Y, Guo P et al (2011) Application of phi29 motor pRNA for targeted therapeutic delivery of siRNA silencing metallothionein-IIA and survivin in ovarian cancers. Mol Ther 19:386–394

    Article  PubMed  CAS  Google Scholar 

  • Thiel KW, Giangrande PH (2009) Therapeutic applications of DNA and RNA aptamers. Oligonucleotides 19:209–222

    Article  PubMed  CAS  Google Scholar 

  • Thiel KW, Giangrande PH (2010) Intracellular delivery of RNA-based therapeutics using aptamers. Ther Deliv 1:849–861

    Article  PubMed  CAS  Google Scholar 

  • Thiel KW, Hernandez LI, Dassie JP et al (2012) Delivery of chemo-sensitizing siRNAs to HER2 + −breast cancer cells using RNA aptamers. Nucleic Acids Res 40:6319–6337

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Tuerk C, Macdougal S, Gold L (1992) RNA pseudoknots that inhibit human immunodeficiency virus type 1 reverse transcriptase. Proc Natl Acad Sci USA 89:6988–6992

    Article  PubMed  CAS  Google Scholar 

  • Wang J, Li G (2011) Aptamers against cell surface receptors: selection, modification and application. Curr Med Chem 18:4107–4116

    Article  PubMed  CAS  Google Scholar 

  • Wang AZ, Bagalkot V, Vasilliou CC et al (2008) Superparamagnetic iron oxide nanoparticle-aptamer bioconjugates for combined prostate cancer imaging and therapy. ChemMedChem 3:1311–1315

    Article  PubMed  CAS  Google Scholar 

  • Wheeler LA, Trifonova R, Vrbanac V et al (2011) Inhibition of HIV transmission in human cervicovaginal explants and humanized mice using CD4 aptamer-siRNA chimeras. J Clin Invest 121:2401–2412

    Article  PubMed  CAS  Google Scholar 

  • Wilen CB, Tilton JC, Doms RW (2012) Molecular mechanisms of HIV entry. Adv Exp Med Biol 726:223–242

    Article  PubMed  CAS  Google Scholar 

  • Wu SY, Mcmillan NA (2009) Lipidic systems for in vivo siRNA delivery. AAPS J 11:639–652

    Article  PubMed  CAS  Google Scholar 

  • Wullner U, Neef I, Eller A et al (2008) Cell-specific induction of apoptosis by rationally designed bivalent aptamer-siRNA transcripts silencing eukaryotic elongation factor 2. Curr Cancer Drug Targets 8:554–565

    Article  PubMed  CAS  Google Scholar 

  • Xiao F, Moll WD, Guo S et al (2005) Binding of pRNA to the N-terminal 14 amino acids of connector protein of bacteriophage phi29. Nucleic Acids Res 33:2640–2649

    Article  PubMed  CAS  Google Scholar 

  • Ye X, Liu Z, Hemida MG et al (2011) Targeted delivery of mutant tolerant anti-coxsackievirus artificial microRNAs using folate conjugated bacteriophage Phi29 pRNA. PLoS One 6:e21215

    Article  PubMed  CAS  Google Scholar 

  • Ye M, Hu J, Peng M et al (2012a) Generating aptamers by cell-SELEX for applications in molecular medicine. Int J Mol Sci 13:3341–3353

    Article  PubMed  CAS  Google Scholar 

  • Ye X, Hemida M, Zhang HM et al (2012b) Current advances in Phi29 pRNA biology and its application in drug delivery. Wiley Interdiscip Rev RNA 3(4):469–481

    Article  PubMed  CAS  Google Scholar 

  • Zhang C, Lee CS, Guo P (1994) The proximate 5′ and 3′ ends of the 120-base viral RNA (pRNA) are crucial for the packaging of bacteriophage phi 29 DNA. Virology 201:77–85

    Article  PubMed  CAS  Google Scholar 

  • Zhang C, Trottier M, Guo P (1995) Circularly permuted viral pRNA active and specific in the packaging of bacteriophage phi 29 DNA. Virology 207:442–451

    Article  PubMed  CAS  Google Scholar 

  • Zhang H, Shu D, Browne M et al (2010) Construction of a laser combiner for dual fluorescent single molecule imaging of pRNA of phi29 DNA packaging motor. Biomed Microdevices 12:97–106

    Article  PubMed  Google Scholar 

  • Zhou J, Rossi JJ (2009) The therapeutic potential of cell-internalizing aptamers. Curr Top Med Chem 9:1144–1157

    Article  PubMed  CAS  Google Scholar 

  • Zhou J, Rossi JJ (2010) Aptamer-targeted cell-specific RNA interference. Silence 1:4

    Article  PubMed  CAS  Google Scholar 

  • Zhou J, Rossi JJ (2011a) Aptamer-targeted RNAi for HIV-1 therapy. Methods Mol Biol 721:355–371

    Article  PubMed  CAS  Google Scholar 

  • Zhou J, Rossi JJ (2011b) Cell-specific aptamer-mediated targeted drug delivery. Oligonucleotides 21:1–10

    Article  PubMed  CAS  Google Scholar 

  • Zhou J, Li H, Li S et al (2008) Novel dual inhibitory function aptamer-siRNA delivery system for HIV-1 therapy. Mol Ther 16:1481–1489

    Article  PubMed  CAS  Google Scholar 

  • Zhou J, Swiderski P, Li H et al (2009) Selection, characterization and application of new RNA HIV gp 120 aptamers for facile delivery of dicer substrate siRNAs into HIV infected cells. Nucleic Acids Res 37:3094–3109

    Article  PubMed  CAS  Google Scholar 

  • Zhou J, Neff CP, Liu X et al (2011a) Systemic administration of combinatorial dsiRNAs via nanoparticles efficiently suppresses HIV-1 infection in humanized mice. Mol Ther 19:2228–2238

    Article  PubMed  CAS  Google Scholar 

  • Zhou J, Shu Y, Guo P et al (2011b) Dual functional RNA nanoparticles containing phi29 motor pRNA and anti-gp120 aptamer for cell-type specific delivery and HIV-1 inhibition. Methods 54:284–294

    Article  PubMed  CAS  Google Scholar 

  • Zhou J, Neff CP, Swiderski P et al (2013) Functional in vivo delivery of multiplexed anti-HIV-1 siRNAs via a chemically synthesized aptamer with a sticky bridge. Mol Ther 21:192–200

    Article  PubMed  CAS  Google Scholar 

  • Zhu Q, Shibata T, Kabashima T et al (2012) Inhibition of HIV-1 protease expression in T cells owing to DNA aptamer-mediated specific delivery of siRNA. Eur J Med Chem 56:396–399

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank Nicholas Snead for critical reading of the manuscript. This work is supported by NCI CA151648 awarded to Peixuan Guo and subcontracted to John J. Rossi.

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  1. Department of Molecular and Cellular Biology, Beckman Research Institute of the City of Hope, Duarte, CA, 91010, USA

    Ka-To Shum & John J. Rossi

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  1. Ka-To Shum
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Correspondence to John J. Rossi .

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  1. Institute of Chemistry/Biochemistry, Free University Berlin, Thielallee 63, Berlin, 14195, Berlin, Germany

    Volker A. Erdmann

  2. Inst. Bioorganic Chemistry, PAN Poznan, ul. Z. Noskowskiego 12/14, Poznan, 61-704, Poland

    Jan Barciszewski

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Shum, KT., Rossi, J.J. (2013). RNA Nanotechnology Approach for Targeted Delivery of RNA Therapeutics Using Cell-Internalizing Aptamers. In: Erdmann, V., Barciszewski, J. (eds) DNA and RNA Nanobiotechnologies in Medicine: Diagnosis and Treatment of Diseases. RNA Technologies. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-36853-0_16

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