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      Aptamers: Uptake mechanisms and intracellular applications

      review-article
      a , a , b , *
      Advanced Drug Delivery Reviews
      Published by Elsevier B.V.
      SELEX, systematic evolution of ligands by exponential enrichment, AML, amiloride, CPZ, chlorpromazine, GEN, genistein, LAMP-1, lysosomal-associated membrane protein 1, ER, endoplasmic reticulum, QD, quantum dots, NP, nanoparticles, TEM, transmission electron microscopy, PRMT5, protein arginine methyltransferase 5, DFHBI, 3,5-difluoro-4-hydroxybenzylidene imidazolinone, TO, thiazole orange, DFHO, 3,5-difluoro-4-hydroxynenzylidene imidazolinone-2-oxime, GFP, green fluorescence protein, E.coli, Escherichia coli, cdiA, cyclic di-AMP, ADP, adenosine di-phosphate, SAM, S-adenosylmethionine, GTP, guanosine 5-triphosphate, C. elegans, Caenorhabditis elegans, EGFP, enhanced green fluorescence protein, snRNA, small nuclear RNA, snRNP, small nuclear protein, apta-FRET, aptamer-based Förster resonance energy transfer, TF, transcription factor, TetR, tetracycline repressor, RNAP, RNA polymerase, RAPs, RNA polymerase binding aptamers, iRAPs, inhibitory RNA polymerase binding aptamers, UTR, Untranslated region, Hsp70, Heat shock protein 70, FOXM1, forkhead box M1, DBD, DNA binding domain, HSP, heat shock factor, NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells, RUNX1, runt-related transcription factor 1, RHD, runt-homology domain, USP14, ubiquitin carboxyl-terminal hydrolase 14, CBFβ, core-binding factor β protein, GPCR, G-protein-coupled receptors, HIV, human immunodeficiency virus, AD, Alzheimer's disease, TGF-β1, transforming growth factor beta 1, CSC, cancer stem cell, HER2, human epidermal growth factor receptor 2, EpCAM, epithelial cell adhesion molecule, MRP1, multidrug resistance-associated protein 1, eIF4A, eukaryotic initiation factor-4A, ATP, adenosine triphosphate, β2AR, β2-adrenoceptor, Sf9, Spodoptera frugiperda 9, cJun, protein that in humans is encoded by the JUN gene, cFos, proto-oncogene that is the human homolog of the retroviral oncogene v-fos, AP-1, activator protein-1, dsRBM, double-stranded RNA binding domain, Aptamer, Endocytosis, Imaging, Gene regulation, Intramers, Allosteric modulation, G-quadruplex

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          Abstract

          The structural flexibility and small size of aptamers enable precise recognition of cellular elements for imaging and therapeutic applications. The process by which aptamers are taken into cells depends on their targets but is typically clathrin-mediated endocytosis or macropinocytosis. After internalization, most aptamers are transported to endosomes, lysosomes, endoplasmic reticulum, Golgi apparatus, and occasionally mitochondria and autophagosomes. Intracellular aptamers, or “intramers,” have versatile functions ranging from intracellular RNA imaging, gene regulation, and therapeutics to allosteric modulation, which we discuss in this review. Immune responses to therapeutic aptamers and the effects of G-quadruplex structure on aptamer function are also discussed.

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          AP-1: a double-edged sword in tumorigenesis.

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            Aptamers as targeted therapeutics: current potential and challenges

            Nucleic acid aptamers offer several advantages over traditional antibodies, but their clinical translation has been delayed by several factors, including insufficient potency, lack of safety data and high production costs. Here, Zhou and Rossi provide an overview of aptamer generation, focusing on recent technological advances and clinical development, as well as challenges and lessons learned.
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              AP-1 function and regulation.

              AP-1 (activating protein-1) is a collective term referring to dimeric transcription factors composed of Jun, Fos or ATF (activating transcription factor) subunits that bind to a common DNA site, the AP-1-binding site. As the complexity of our knowledge of AP-1 factors has increased, our understanding of their physiological function has decreased. This trend, however, is beginning to be reversed due to the recent studies of gene-knockout mice and cell lines deficient in specific AP-1 components. Such studies suggest that different AP-1 factors may regulate different target genes and thus execute distinct biological functions. Also, the involvement of AP-1 factors in functions such as cell proliferation and survival has been made somewhat clearer as a result of such studies. In addition, there has been considerable progress in understanding some of the mechanisms and signaling pathways involved in the regulation of AP-1 activity. In addition to regulation by heterodimerization between Jun, Fos and ATF proteins, AP-1 activity is regulated through interactions with specific protein kinases and a variety of transcriptional coactivators.
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                Author and article information

                Contributors
                Journal
                Adv Drug Deliv Rev
                Adv. Drug Deliv. Rev
                Advanced Drug Delivery Reviews
                Published by Elsevier B.V.
                0169-409X
                1872-8294
                6 July 2018
                September 2018
                6 July 2018
                : 134
                : 22-35
                Affiliations
                [a ]Department of Molecular and Cellular Biology, Beckman Research Institute of City of Hope, Duarte, CA, USA
                [b ]Irell and Manella Graduate School of Biological Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA
                Author notes
                [* ]Corresponding author at: 1500 E. Duarte Rd, Duarte, CA, USA. jrossi@ 123456coh.org
                Article
                S0169-409X(18)30167-4
                10.1016/j.addr.2018.07.003
                7126894
                29981799
                d140df29-78ec-4497-be04-5ab9c688e9c8
                © 2018 Published by Elsevier B.V.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 12 January 2018
                : 6 June 2018
                : 4 July 2018
                Categories
                Article

                selex, systematic evolution of ligands by exponential enrichment,aml, amiloride,cpz, chlorpromazine,gen, genistein,lamp-1, lysosomal-associated membrane protein 1,er, endoplasmic reticulum,qd, quantum dots,np, nanoparticles,tem, transmission electron microscopy,prmt5, protein arginine methyltransferase 5,dfhbi, 3,5-difluoro-4-hydroxybenzylidene imidazolinone,to, thiazole orange,dfho, 3,5-difluoro-4-hydroxynenzylidene imidazolinone-2-oxime,gfp, green fluorescence protein,e.coli, escherichia coli,cdia, cyclic di-amp,adp, adenosine di-phosphate,sam, s-adenosylmethionine,gtp, guanosine 5-triphosphate,c. elegans, caenorhabditis elegans,egfp, enhanced green fluorescence protein,snrna, small nuclear rna,snrnp, small nuclear protein,apta-fret, aptamer-based förster resonance energy transfer,tf, transcription factor,tetr, tetracycline repressor,rnap, rna polymerase,raps, rna polymerase binding aptamers,iraps, inhibitory rna polymerase binding aptamers,utr, untranslated region,hsp70, heat shock protein 70,foxm1, forkhead box m1,dbd, dna binding domain,hsp, heat shock factor,nf-κb, nuclear factor kappa-light-chain-enhancer of activated b cells,runx1, runt-related transcription factor 1,rhd, runt-homology domain,usp14, ubiquitin carboxyl-terminal hydrolase 14,cbfβ, core-binding factor β protein,gpcr, g-protein-coupled receptors,hiv, human immunodeficiency virus,ad, alzheimer's disease,tgf-β1, transforming growth factor beta 1,csc, cancer stem cell,her2, human epidermal growth factor receptor 2,epcam, epithelial cell adhesion molecule,mrp1, multidrug resistance-associated protein 1,eif4a, eukaryotic initiation factor-4a,atp, adenosine triphosphate,β2ar, β2-adrenoceptor,sf9, spodoptera frugiperda 9,cjun, protein that in humans is encoded by the jun gene,cfos, proto-oncogene that is the human homolog of the retroviral oncogene v-fos,ap-1, activator protein-1,dsrbm, double-stranded rna binding domain,aptamer,endocytosis,imaging,gene regulation,intramers,allosteric modulation,g-quadruplex
                selex, systematic evolution of ligands by exponential enrichment, aml, amiloride, cpz, chlorpromazine, gen, genistein, lamp-1, lysosomal-associated membrane protein 1, er, endoplasmic reticulum, qd, quantum dots, np, nanoparticles, tem, transmission electron microscopy, prmt5, protein arginine methyltransferase 5, dfhbi, 3,5-difluoro-4-hydroxybenzylidene imidazolinone, to, thiazole orange, dfho, 3,5-difluoro-4-hydroxynenzylidene imidazolinone-2-oxime, gfp, green fluorescence protein, e.coli, escherichia coli, cdia, cyclic di-amp, adp, adenosine di-phosphate, sam, s-adenosylmethionine, gtp, guanosine 5-triphosphate, c. elegans, caenorhabditis elegans, egfp, enhanced green fluorescence protein, snrna, small nuclear rna, snrnp, small nuclear protein, apta-fret, aptamer-based förster resonance energy transfer, tf, transcription factor, tetr, tetracycline repressor, rnap, rna polymerase, raps, rna polymerase binding aptamers, iraps, inhibitory rna polymerase binding aptamers, utr, untranslated region, hsp70, heat shock protein 70, foxm1, forkhead box m1, dbd, dna binding domain, hsp, heat shock factor, nf-κb, nuclear factor kappa-light-chain-enhancer of activated b cells, runx1, runt-related transcription factor 1, rhd, runt-homology domain, usp14, ubiquitin carboxyl-terminal hydrolase 14, cbfβ, core-binding factor β protein, gpcr, g-protein-coupled receptors, hiv, human immunodeficiency virus, ad, alzheimer's disease, tgf-β1, transforming growth factor beta 1, csc, cancer stem cell, her2, human epidermal growth factor receptor 2, epcam, epithelial cell adhesion molecule, mrp1, multidrug resistance-associated protein 1, eif4a, eukaryotic initiation factor-4a, atp, adenosine triphosphate, β2ar, β2-adrenoceptor, sf9, spodoptera frugiperda 9, cjun, protein that in humans is encoded by the jun gene, cfos, proto-oncogene that is the human homolog of the retroviral oncogene v-fos, ap-1, activator protein-1, dsrbm, double-stranded rna binding domain, aptamer, endocytosis, imaging, gene regulation, intramers, allosteric modulation, g-quadruplex

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