Articoli di riviste: "Antisense nucleic acids"

1

Goodchild, John. "Antisense nucleic acids and proteins". Cell Biophysics 18, n. 3 (giugno 1991): 295–96. http://dx.doi.org/10.1007/bf02989820.

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Razzak, Mina. "Antisense nucleic acids—tough delivery". Nature Reviews Urology 10, n. 12 (19 novembre 2013): 681. http://dx.doi.org/10.1038/nrurol.2013.271.

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Soomets, Ursel. "Antisense properties of peptide nucleic acids". Frontiers in Bioscience 4, n. 1-3 (1999): d782. http://dx.doi.org/10.2741/soomets.

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Langel, Ülo. "Antisense properties of peptide nucleic acids". Frontiers in Bioscience 4, n. 4 (1999): d782–786. http://dx.doi.org/10.2741/a394.

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5

Tonkinson, J. L., e C. A. Stein. "Antisense Nucleic Acids — Prospects for Antiviral Intervention". Antiviral Chemistry and Chemotherapy 4, n. 4 (agosto 1993): 193–200. http://dx.doi.org/10.1177/095632029300400401.

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Abstract (sommario):

Antisense oligodeoxynucleotides are a promising new class of antiviral agent. Because they bind in a sequence-specific manner to complementary regions of mRNA, oligos can inhibit gene expression in a sequence-specific manner. The ‘antisense’ approach has been used successfully to block cellular expression and replication of several viruses including Human Immunodeficiency Virus-1 (HIV-1), and Herpes Simplex Virus (HSV). However, the antiviral effect of oligodeoxynucleotides is not limited to sequence-specific inhibition of gene expression. Non sequence-specific effects are frequently observed, presumably as a result of their properties as polyanions. Occasionally (e.g. for HIV-1) these non sequence-specific effects are also therapeutic. The prospects for antisense oligodeoxynucleotide therapy for viral disease are discussed.

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Morihiro, Kunihiko, Yuuya Kasahara e Satoshi Obika. "Biological applications of xeno nucleic acids". Molecular BioSystems 13, n. 2 (2017): 235–45. http://dx.doi.org/10.1039/c6mb00538a.

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Malcolm, Alan D. B. "Uses of antisense nucleic acids — an introduction". Biochemical Society Transactions 20, n. 4 (1 novembre 1992): 745–46. http://dx.doi.org/10.1042/bst0200745.

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8

Flores, Maria Vega C., David Atkins, Thomas Stanley Stewart, Arthur van Aerschot e Piet Herdewijn. "Antimalarial antisense activity of hexitol nucleic acids". Parasitology Research 85, n. 10 (24 agosto 1999): 864–66. http://dx.doi.org/10.1007/s004360050647.

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9

Nielsen, Peter. "Targeting structured nucleic acids with antisense agents ▾". Drug Discovery Today 8, n. 10 (maggio 2003): 440. http://dx.doi.org/10.1016/s1359-6446(03)02702-8.

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Li, Hui, Bohan Zhang, Xueguang Lu, Xuyu Tan, Fei Jia, Yue Xiao, Zehong Cheng et al. "Molecular spherical nucleic acids". Proceedings of the National Academy of Sciences 115, n. 17 (9 aprile 2018): 4340–44. http://dx.doi.org/10.1073/pnas.1801836115.

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Herein, we report a class of molecular spherical nucleic acid (SNA) nanostructures. These nano-sized single molecules are synthesized from T8 polyoctahedral silsesquioxane and buckminsterfullerene C60 scaffolds, modified with 8 and 12 pendant DNA strands, respectively. These conjugates have different DNA surface densities and thus exhibit different levels of nuclease resistance, cellular uptake, and gene regulation capabilities; the properties displayed by the C60 SNA conjugate are closer to those of conventional and prototypical gold nanoparticle SNAs. Importantly, the C60 SNA can serve as a single entity (no transfection agent required) antisense agent to efficiently regulate gene expression. The realization of molecularly pure forms of SNAs will open the door for studying the interactions of such structures with ligands and living cells with a much greater degree of control than the conventional polydisperse forms of SNAs.

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Yamamoto, Tsuyoshi. "Development of Antisense Oligonucleotides with Bridged Nucleic Acids". Drug Delivery System 35, n. 1 (25 gennaio 2020): 82–83. http://dx.doi.org/10.2745/dds.35.82.

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Zaslavsky, Alexander, Mackenzie Adams, Xiu Cao, Adriana Yamaguchi, James Henderson, Peter Busch-Østergren, Aaron Udager et al. "Antisense oligonucleotides and nucleic acids generate hypersensitive platelets". Thrombosis Research 200 (aprile 2021): 64–71. http://dx.doi.org/10.1016/j.thromres.2021.01.006.

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Burnham, Martin, e Yinduo Ji. "Antisense Peptide Nucleic Acids in Antibacterial Drug Discovery". Molecular Therapy 10, n. 4 (ottobre 2004): 614–15. http://dx.doi.org/10.1016/j.ymthe.2004.09.005.

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14

Baulcombe, David. "Antisense nucleic acids and proteins: Fundamentals and applications". Trends in Genetics 9, n. 3 (marzo 1993): 94–95. http://dx.doi.org/10.1016/0168-9525(93)90232-7.

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15

Hanvey, J., N. Peffer, J. Bisi, S. Thomson, R. Cadilla, J. Josey, D. Ricca et al. "Antisense and antigene properties of peptide nucleic acids". Science 258, n. 5087 (27 novembre 1992): 1481–85. http://dx.doi.org/10.1126/science.1279811.

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16

Zimmer, Ch. "Antisense Nucleic Acids and Protein: Fundamentals and Applications." Journal of Electroanalytical Chemistry 342, n. 2 (aprile 1992): 253–54. http://dx.doi.org/10.1016/0022-0728(92)85072-b.

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Zimmer, Ch. "Antisense Nucleic Acids and Protein: Fundamentals and Applications." Bioelectrochemistry and Bioenergetics 27, n. 2 (aprile 1992): 253–54. http://dx.doi.org/10.1016/0302-4598(92)87065-3.

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Kearney, Phil, Majken Westergaard, Henrik F. Hansen, Ellen M. Staarup, Troels Koch, Henrik Ørum e Jens Bo Hansen. "siRNA Versus Antisense Locked Nucleic Acids: Stay Single!." Blood 106, n. 11 (16 novembre 2005): 614. http://dx.doi.org/10.1182/blood.v106.11.614.614.

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Abstract Much discussion has centred around the utility and benefits of siRNA in both target validation and as a therapeutic option. This has been driven by significant publications including that of Soutcheck et al (Nature432, 173–177 2004), which demonstrated liver targeting as well as in vivo efficacy when siRNA against ApoB was tethered to a cholesterol moiety. Santaris Pharma has developed a third generation nucleic acid chemistry referred to as locked nucleic acid (LNA) which delivers unmatched affinity and stabiliy benefits, largely overcoming the drawbacks associated with traditional antisense molecules. We therefore sought to compare this chemistry with targets which siRNA has been successfully used in in vivo/in vitro settings. The same motif used in the Soutcheck study was targeted with a LNA molecule, and the free siRNA activity was compared to the cholesterol linked and free LNA molecules in their ability ot down regulate ApoB expression. LNA (SPC3197) inhibited ApoB expression by 90% while at an equimolar concentration siRNA was ineffective in the liver and jejunum. Cholesterol linked siRNA was only effective in the jejunum (c50% reduction in mRNA) Fig1. Only the LNA mediated inhibition of ApoB expression was paralleled by a drop in serum cholesterol in the host animal. In a second model siRNA molecules targeting Hif-1a mRNA (Yu et al Lab Invest84, 553–561 2004) were compared to our lead LNA molecule targeting Hif-1a, SPC2968. Interestingly in in vitro analyses these 2 molecules were equally effective. However in a murine model the increased half life of the LNA molecules translated to a potent inhibition of Hif-1a as measured by QPCR. This effect was noted in jejunum and liver, and persisted for at least 4 days. Hif-1a inhibition mediated by siRNA was not seen in any tissue analysed (Fig 2). Finally a 3rd molecule targeting Bcl-2 has entered clinical Phase 1 trials, and data will be presented documenting its improved affinity and stabitily in relation to competitor molecules such as Genasense. Figure Figure

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19

Neidle, Stephen. "Antisense Nucleic Acids and Proteins: Fundamentals and Applications". International Journal of Biological Macromolecules 16, n. 2 (aprile 1994): 110. http://dx.doi.org/10.1016/0141-8130(94)90025-6.

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Hélène, C. "Control of oncogene expression by antisense nucleic acids". European Journal of Cancer 30, n. 11 (gennaio 1994): 1721–26. http://dx.doi.org/10.1016/0959-8049(93)e0352-q.

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21

Jani, Saumya, Maria Soledad Ramirez e Marcelo E. Tolmasky. "Silencing Antibiotic Resistance with Antisense Oligonucleotides". Biomedicines 9, n. 4 (12 aprile 2021): 416. http://dx.doi.org/10.3390/biomedicines9040416.

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Abstract (sommario):

Antisense technologies consist of the utilization of oligonucleotides or oligonucleotide analogs to interfere with undesirable biological processes, commonly through inhibition of expression of selected genes. This field holds a lot of promise for the treatment of a very diverse group of diseases including viral and bacterial infections, genetic disorders, and cancer. To date, drugs approved for utilization in clinics or in clinical trials target diseases other than bacterial infections. Although several groups and companies are working on different strategies, the application of antisense technologies to prokaryotes still lags with respect to those that target other human diseases. In those cases where the focus is on bacterial pathogens, a subset of the research is dedicated to produce antisense compounds that silence or reduce expression of antibiotic resistance genes. Therefore, these compounds will be adjuvants administered with the antibiotic to which they reduce resistance levels. A varied group of oligonucleotide analogs like phosphorothioate or phosphorodiamidate morpholino residues, as well as peptide nucleic acids, locked nucleic acids and bridge nucleic acids, the latter two in gapmer configuration, have been utilized to reduce resistance levels. The major mechanisms of inhibition include eliciting cleavage of the target mRNA by the host’s RNase H or RNase P, and steric hindrance. The different approaches targeting resistance to β-lactams include carbapenems, aminoglycosides, chloramphenicol, macrolides, and fluoroquinolones. The purpose of this short review is to summarize the attempts to develop antisense compounds that inhibit expression of resistance to antibiotics.

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Malik, Shipra, W. Mark Saltzman e Raman Bahal. "Extracellular vesicles mediated exocytosis of antisense peptide nucleic acids". Molecular Therapy - Nucleic Acids 25 (settembre 2021): 302–15. http://dx.doi.org/10.1016/j.omtn.2021.07.018.

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23

Kurreck, J. "Design of antisense oligonucleotides stabilized by locked nucleic acids". Nucleic Acids Research 30, n. 9 (1 maggio 2002): 1911–18. http://dx.doi.org/10.1093/nar/30.9.1911.

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Hammond, Scott M. "MicroRNA therapeutics: a new niche for antisense nucleic acids". Trends in Molecular Medicine 12, n. 3 (marzo 2006): 99–101. http://dx.doi.org/10.1016/j.molmed.2006.01.004.

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25

Herdewijn, P. "Conformationally restricted carbohydrate-modified nucleic acids and antisense technology". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression 1489, n. 1 (dicembre 1999): 167–79. http://dx.doi.org/10.1016/s0167-4781(99)00152-9.

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26

Wahlestedt, C., P. Salmi, L. Good, J. Kela, T. Johnsson, T. Hokfelt, C. Broberger et al. "Potent and nontoxic antisense oligonucleotides containing locked nucleic acids". Proceedings of the National Academy of Sciences 97, n. 10 (9 maggio 2000): 5633–38. http://dx.doi.org/10.1073/pnas.97.10.5633.

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27

Aerschot Van, Arthur, Ilse Verheggen, Chris Hendrix e Piet Herdewijn. "1,5-Anhydrohexitol Nucleic Acids, a New Promising Antisense Construct". Angewandte Chemie International Edition in English 34, n. 12 (7 luglio 1995): 1338–39. http://dx.doi.org/10.1002/anie.199513381.

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28

Lin, Mengsi, Xinyi Hu, Shiyi Chang, Yan Chang, Wenjun Bian, Ruikun Hu, Jing Wang, Qingwen Zhu e Jiaying Qiu. "Advances of Antisense Oligonucleotide Technology in the Treatment of Hereditary Neurodegenerative Diseases". Evidence-Based Complementary and Alternative Medicine 2021 (10 giugno 2021): 1–9. http://dx.doi.org/10.1155/2021/6678422.

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Abstract (sommario):

Antisense nucleic acids are single-stranded oligonucleotides that have been specially chemically modified, which can bind to RNA expressed by target genes through base complementary pairing and affect protein synthesis at the level of posttranscriptional processing or protein translation. In recent years, the application of antisense nucleic acid technology in the treatment of neuromuscular diseases has made remarkable progress. In 2016, the US FDA approved two antisense nucleic acid drugs for the treatment of Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA), and the development to treat other neurodegenerative diseases has also entered the clinical stage. Therefore, ASO represents a treatment with great potential. The article will summarize ASO therapies in terms of mechanism of action, chemical modification, and administration methods and analyze their role in several common neurodegenerative diseases, such as SMA, DMD, and amyotrophic lateral sclerosis (ALS). This article systematically summarizes the great potential of antisense nucleic acid technology in the treatment of hereditary neurodegenerative diseases.

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Perche, Federico, Tony Le Gall, Tristan Montier, Chantal Pichon e Jean-Marc Malinge. "Cardiolipin-Based Lipopolyplex Platform for the Delivery of Diverse Nucleic Acids into Gram-Negative Bacteria". Pharmaceuticals 12, n. 2 (28 maggio 2019): 81. http://dx.doi.org/10.3390/ph12020081.

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Antibiotic resistance is a growing public health concern. Because only a few novel classes of antibiotics have been developed in the last 40 years, such as the class of oxazolidinones, new antibacterial strategies are urgently needed (Coates, A.R. et al., 2011). Nucleic acid-based antibiotics are a new type of antimicrobials. However, free nucleic acids cannot spontaneously cross the bacterial cell wall and membrane; consequently, their intracellular delivery into bacteria needs to be assisted. Here, we introduce an original lipopolyplex system named liposome polymer nucleic acid (LPN), capable of versatile nucleic acid delivery into bacteria. We characterized LPN formed with significant therapeutic nucleic acids: 11 nt antisense single-stranded (ss) DNA and double-stranded (ds) DNA of 15 and 95 base pairs (bp), 9 kbp plasmid DNA (pDNA), and 1000 nt ssRNA. All these complexes were efficiently internalized by two different bacterial species, i.e., Escherichia coli and Pseudomonas aeruginosa, as shown by flow cytometry. Consistent with intracellular delivery, LPN prepared with an antisense oligonucleotide and directed against an essential gene, induced specific and important bacterial growth inhibition likely leading to a bactericidal effect. Our findings indicate that LPN is a versatile platform for efficient delivery of diverse nucleic acids into Gram-negative bacteria.

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Le, Bao T., Vyacheslav V. Filichev e Rakesh N. Veedu. "Investigation of twisted intercalating nucleic acid (TINA)-modified antisense oligonucleotides for splice modulation by induced exon-skipping in vitro". RSC Advances 6, n. 97 (2016): 95169–72. http://dx.doi.org/10.1039/c6ra22346j.

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Traykovska, Martina, Sjoerd Miedema e Robert Penchovsky. "Clinical Trials of Functional Nucleic Acids". International Journal of Biomedical and Clinical Engineering 7, n. 2 (luglio 2018): 46–60. http://dx.doi.org/10.4018/ijbce.2018070104.

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This chapter describes how functional nucleic acids, such as aptamers, antisense oligonucleotides (ASOs), small interfering (si) RNAs, and ribozymes are considered by some researchers as valuable tools to develop therapeutic agents. They have not been particularly fast in reaching the market as medicines, due to endogenous barriers to extracellular trafficking and cellular uptake of nucleic acids and their inherent instability when applied in vivo. However, research carried out by the nucleic acid engineering community and pharmaceutical companies to circumvent these obstacles has led to the approval of a few aptamers and ASOs as drugs. Nucleic acid therapeutics are usually administered locally to diseased tissue. The drug candidates currently in clinical trials commonly use the same administration methods as previously licensed nucleic acid therapeutics. These administration techniques carry their own safety risks and advantages. In this article, the present state is discussed and prospective options for the use ASOs and aptamers as drugs are listed.

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Nielsen, Peter E. "Addressing the challenges of cellular delivery and bioavailability of peptide nucleic acids (PNA)". Quarterly Reviews of Biophysics 38, n. 4 (novembre 2005): 345–50. http://dx.doi.org/10.1017/s0033583506004148.

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1. Introduction 3452. Peptide nucleic acid (PNA) 3463. ‘Cell penetrating peptides’ (CPPs) 3464. Endosomal escape 3475. Cellular delivery of PNA 3476.In vivobioavailability of PNA 3497. References 350Recent results on the cellular delivery of antisense peptide nucleic acids (PNA) via peptide conjugation is briefly discussed, in particular in the context of endosomal entrapment and escape.

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Shen, Yuefei, Ritu Shrestha, Aida Ibricevic, Sean P. Gunsten, Michael J. Welch, Karen L. Wooley, Steven L. Brody, John-Stephen A. Taylor e Yongjian Liu. "Antisense peptide nucleic acid-functionalized cationic nanocomplex for in vivo mRNA detection". Interface Focus 3, n. 3 (6 giugno 2013): 20120059. http://dx.doi.org/10.1098/rsfs.2012.0059.

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Acute lung injury (ALI) is a complex syndrome with many aetiologies, resulting in the upregulation of inflammatory mediators in the host, followed by dyspnoea, hypoxemia and pulmonary oedema. A central mediator is inducible nitric oxide synthase (iNOS) that drives the production of NO and continued inflammation. Thus, it is useful to have diagnostic and therapeutic agents for targeting iNOS expression. One general approach is to target the precursor iNOS mRNA with antisense nucleic acids. Peptide nucleic acids (PNAs) have many advantages that make them an ideal platform for development of antisense theranostic agents. Their membrane impermeability, however, limits biological applications. Here, we report the preparation of an iNOS imaging probe through electrostatic complexation between a radiolabelled antisense PNA-YR 9 · oligodeoxynucleotide (ODN) hybrid and a cationic shell-cross-linked knedel-like nanoparticle (cSCK). The Y (tyrosine) residue was used for 123 I radiolabelling, whereas the R 9 (arginine 9 ) peptide was included to facilitate cell exit of untargeted PNA. Complete binding of the antisense PNA-YR 9 · ODN hybrid to the cSCK was achieved at an 8 : 1 cSCK amine to ODN phosphate (N/P) ratio by a gel retardation assay. The antisense PNA-YR 9 · ODN · cSCK nanocomplexes efficiently entered RAW264.7 cells, whereas the PNA-YR 9 · ODN alone was not taken up. Low concentrations of 123 I-labelled antisense PNA-YR 9 · ODN complexed with cSCK showed significantly higher retention of radioactivity when iNOS was induced in lipopolysaccharide+interferon-γ-activated RAW264.7 cells when compared with a mismatched PNA. Moreover, statistically, greater retention of radioactivity from the antisense complex was also observed in vivo in an iNOS-induced mouse lung after intratracheal administration of the nanocomplexes. This study demonstrates the specificity and sensitivity by which the radiolabelled nanocomplexes can detect iNOS mRNA in vitro and in vivo and their potential for early diagnosis of ALI.

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Nielsen, Peter E. "Peptide nucleic acids as antibacterial agents via the antisense principle". Expert Opinion on Investigational Drugs 10, n. 2 (febbraio 2001): 331–41. http://dx.doi.org/10.1517/13543784.10.2.331.

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Van Aerschot, A., A. Marchand, G. Schepers, W. Van den Eynde, J. Rozenski, R. Busson e P. Herdewijn. "Methylated Hexitol Nucleic Acids, Towards Congeners with Improved Antisense Potential". Nucleosides, Nucleotides and Nucleic Acids 22, n. 5-8 (ottobre 2003): 1227–29. http://dx.doi.org/10.1081/ncn-120022842.

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Chiarantini, Laura, Aurora Cerasi, Alessandra Fraternale, Enrico Millo, Umberto Benatti, Katia Sparnacci, Michele Laus, Marco Ballestri e Luisa Tondelli. "Comparison of novel delivery systems for antisense peptide nucleic acids". Journal of Controlled Release 109, n. 1-3 (dicembre 2005): 24–36. http://dx.doi.org/10.1016/j.jconrel.2005.09.013.

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Lee, Hyung Tae, Se Kye Kim e Jang Won Yoon. "Antisense peptide nucleic acids as a potential anti-infective agent". Journal of Microbiology 57, n. 6 (27 maggio 2019): 423–30. http://dx.doi.org/10.1007/s12275-019-8635-4.

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Fattal, Elias, e Amélie Bochot. "Ocular delivery of nucleic acids: antisense oligonucleotides, aptamers and siRNA". Advanced Drug Delivery Reviews 58, n. 11 (novembre 2006): 1203–23. http://dx.doi.org/10.1016/j.addr.2006.07.020.

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Hashemzadeh, Mohammad S. "Peptide nucleic acid (PNA) as a novel tool in the detection and treatment of biological threatening diseases". Romanian Journal of Military Medicine 124, n. 1 (2 gennaio 2021): 54–60. http://dx.doi.org/10.55453/rjmm.2021.124.1.7.

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Abstract (sommario):

"Abstract: Peptide Nucleic Acids (PNAs) are nanostructures similar to nucleic acid molecules (synthetic DNA/RNA analogs) wherein the negatively charged backbone (sugar-phosphate) present in DNA/RNA molecules is replaced by a backbone without polyamide or peptide charge. Later, it was found that PNAs containing both purine and pyrimidine bases form highly stable duplexes with DNA and RNA. Although it is not as stable as 2PNA/DNA triplexes containing a homopyrimidine strand, it is still more stable than DNA/DNA and/or DNA/RNA duplexes. The unique characteristics of PNAs add new aspects to these nanostructures relative to conventional analogs to make them appropriate for molecular biology studies. The most important applications include the use of these nanostructures in the detection and treatment of diseases caused by threatening biological agents using the antisense/antigen technology and as genetic regulator drugs. Keywords: Peptide Nucleic Acids (PNAs), synthetic DNA analog, genetic regulator drugs, antisense-antigen technology"

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Yamamoto, Tsuyoshi, Aiko Yahara, Reiko Waki, Hidenori Yasuhara, Fumito Wada, Mariko Harada-Shiba e Satoshi Obika. "Amido-bridged nucleic acids with small hydrophobic residues enhance hepatic tropism of antisense oligonucleotides in vivo". Organic & Biomolecular Chemistry 13, n. 12 (2015): 3757–65. http://dx.doi.org/10.1039/c5ob00242g.

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Mercurio, Silvia, Silvia Cauteruccio, Raoul Manenti, Simona Candiani, Giorgio Scarì, Emanuela Licandro e Roberta Pennati. "Exploring miR-9 Involvement in Ciona intestinalis Neural Development Using Peptide Nucleic Acids". International Journal of Molecular Sciences 21, n. 6 (15 marzo 2020): 2001. http://dx.doi.org/10.3390/ijms21062001.

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Abstract (sommario):

The microRNAs are small RNAs that regulate gene expression at the post-transcriptional level and can be involved in the onset of neurodegenerative diseases and cancer. They are emerging as possible targets for antisense-based therapy, even though the in vivo stability of miRNA analogues is still questioned. We tested the ability of peptide nucleic acids, a novel class of nucleic acid mimics, to downregulate miR-9 in vivo in an invertebrate model organism, the ascidian Ciona intestinalis, by microinjection of antisense molecules in the eggs. It is known that miR-9 is a well-conserved microRNA in bilaterians and we found that it is expressed in epidermal sensory neurons of the tail in the larva of C. intestinalis. Larvae developed from injected eggs showed a reduced differentiation of tail neurons, confirming the possibility to use peptide nucleic acid PNA to downregulate miRNA in a whole organism. By identifying putative targets of miR-9, we discuss the role of this miRNA in the development of the peripheral nervous system of ascidians.

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Nawrot, Barbara. "Targeting BACE with small inhibitory nucleic acids - a future for Alzheimer's disease therapy?" Acta Biochimica Polonica 51, n. 2 (30 giugno 2004): 431–44. http://dx.doi.org/10.18388/abp.2004_3582.

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beta-Secretase, a beta-site amyloid precursor protein (APP) cleaving enzyme (BACE), participates in the secretion of beta-amyloid peptides (Abeta), the major components of the toxic amyloid plaques found in the brains of patients with Alzheimer's disease (AD). According to the amyloid hypothesis, accumulation of Abeta is the primary influence driving AD pathogenesis. Lowering of Abeta secretion can be achieved by decreasing BACE activity rather than by down-regulation of the APP substrate protein. Therefore, beta-secretase is a primary target for anti-amyloid therapeutic drug design. Several approaches have been undertaken to find an effective inhibitor of human beta-secretase activity, mostly in the field of peptidomimetic, non-cleavable substrate analogues. This review describes strategies targeting BACE mRNA recognition and its down-regulation based on the antisense action of small inhibitory nucleic acids (siNAs). These include antisense oligonucleotides, catalytic nucleic acids - ribozymes and deoxyribozymes - as well as small interfering RNAs (siRNAs). While antisense oligonucleotides were first used to identify an aspartyl protease with beta-secretase activity, all the strategies now demonstrate that siNAs are able to inhibit BACE gene expression in a sequence-specific manner, measured both at the level of its mRNA and at the level of protein. Moreover, knock-down of BACE reduces the intra- and extracellular population of Abeta40 and Abeta42 peptides. An anti-amyloid effect of siNAs is observed in a wide spectrum of cell lines as well as in primary cortical neurons. Thus targeting BACE with small inhibitory nucleic acids may be beneficial for the treatment of Alzheimer's disease and for future drug design.

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Zhang, Yumin, Jiang He, Guozheng Liu, Jean-Luc Venderheyden, Suresh Gupta, Mary Rusckowski e Donald J. Hnatowich. "Initial observations of 99mTc labelled locked nucleic acids for antisense targeting". Nuclear Medicine Communications 25, n. 11 (novembre 2004): 1113–18. http://dx.doi.org/10.1097/00006231-200411000-00008.

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Eldrup, Anne B., e Peter E. Nielsen. "ChemInform Abstract: Peptide Nucleic Acids: Potential as Antisense and Antigene Drugs". ChemInform 31, n. 15 (9 giugno 2010): no. http://dx.doi.org/10.1002/chin.200015249.

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VAN AERSCHOT, A., I. VERHEGGEN, C. HENDRIX e P. HERDEWIJN. "ChemInform Abstract: 1,5-Anhydrohexitol Nucleic Acids, a New Promising Antisense Construct." ChemInform 26, n. 40 (17 agosto 2010): no. http://dx.doi.org/10.1002/chin.199540265.

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46

Kurupati, Prathiba, Kevin Shyong Wei Tan, Gamini Kumarasinghe e Chit Laa Poh. "Inhibition of Gene Expression and Growth by Antisense Peptide Nucleic Acids in a Multiresistant β-Lactamase-Producing Klebsiella pneumoniae Strain". Antimicrobial Agents and Chemotherapy 51, n. 3 (11 dicembre 2006): 805–11. http://dx.doi.org/10.1128/aac.00709-06.

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ABSTRACT Klebsiella pneumoniae causes common and severe hospital- and community-acquired infections with a high incidence of multidrug resistance. The emergence and spread of β-lactamase-producing K. pneumoniae strains highlight the need to develop new therapeutic strategies. In this study, we developed antisense peptide nucleic acids (PNAs) conjugated to the (KFF)3K peptide and investigated whether they could mediate gene-specific antisense effects in K. pneumoniae. No outer membrane permeabilization was observed with antisense PNAs when used alone. Antisense peptide-PNAs targeted at two essential genes, gyrA and ompA, were found to be growth inhibitory at concentrations of 20 μM and 40 μM, respectively. Mismatched antisense peptide-PNAs with sequence variations of the gyrA and ompA genes when used as controls were not growth inhibitory. Bactericidal effects exerted by peptide-anti-gyrA PNA and peptide-anti-ompA PNA on cells were observed within 6 h of treatment. The antisense peptide-PNAs specifically inhibited expression of DNA gyrase subunit A and OmpA from the respective targeted genes in a dose-dependent manner. Both antisense peptide-PNAs cured IMR90 cell cultures that were infected with K. pneumoniae (104 CFU) in a dose-dependent manner without any noticeable toxicity to the human cells.

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Prajapati, Rama, e Álvaro Somoza. "Albumin Nanostructures for Nucleic Acid Delivery in Cancer: Current Trend, Emerging Issues, and Possible Solutions". Cancers 13, n. 14 (9 luglio 2021): 3454. http://dx.doi.org/10.3390/cancers13143454.

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Cancer is one of the major health problems worldwide, and hence, suitable therapies with enhanced efficacy and reduced side effects are desired. Gene therapy, involving plasmids, small interfering RNAs, and antisense oligonucleotides have been showing promising potential in cancer therapy. In recent years, the preparation of various carriers for nucleic acid delivery to the tumor sites is gaining attention since intracellular and extracellular barriers impart major challenges in the delivery of naked nucleic acids. Albumin is a versatile protein being used widely for developing carriers for nucleic acids. It provides biocompatibility, tumor specificity, the possibility for surface modification, and reduces toxicity. In this review, the advantages of using nucleic acids in cancer therapy and the challenges associated with their delivery are presented. The focus of this article is on the different types of albumin nanocarriers, such as nanoparticles, polyplexes, and nanoconjugates, employed to overcome the limitations of the direct use of nucleic acids in vivo. This review also highlights various approaches for the modification of the surface of albumin to enhance its transfection efficiency and targeted delivery in the tumor sites.

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Wojciechowska, Monika, Marcin Równicki, Adam Mieczkowski, Joanna Miszkiewicz e Joanna Trylska. "Antibacterial Peptide Nucleic Acids—Facts and Perspectives". Molecules 25, n. 3 (28 gennaio 2020): 559. http://dx.doi.org/10.3390/molecules25030559.

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Antibiotic resistance is an escalating, worldwide problem. Due to excessive use of antibiotics, multidrug-resistant bacteria have become a serious threat and a major global healthcare problem of the 21st century. This fact creates an urgent need for new and effective antimicrobials. The common strategies for antibiotic discovery are based on either modifying existing antibiotics or screening compound libraries, but these strategies have not been successful in recent decades. An alternative approach could be to use gene-specific oligonucleotides, such as peptide nucleic acid (PNA) oligomers, that can specifically target any single pathogen. This approach broadens the range of potential targets to any gene with a known sequence in any bacterium, and could significantly reduce the time required to discover new antimicrobials or their redesign, if resistance arises. We review the potential of PNA as an antibacterial molecule. First, we describe the physicochemical properties of PNA and modifications of the PNA backbone and nucleobases. Second, we review the carriers used to transport PNA to bacterial cells. Furthermore, we discuss the PNA targets in antibacterial studies focusing on antisense PNA targeting bacterial mRNA and rRNA.

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Singh, Kuljit, e Ipsita Roy. "Nucleic Acid Therapeutics in Huntington’s Disease". Recent Patents on Biotechnology 13, n. 3 (6 agosto 2019): 187–206. http://dx.doi.org/10.2174/1872208313666190208163714.

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Background: Protein misfolding is a critical factor in the progression of a large number of neurodegenerative diseases. The incorrectly folded protein is prone to aggregation, leading to aberrant interaction with other cellular proteins, elevated oxidative stress, impaired cellular machinery, finally resulting in cell death. Due to its monogenic origin, Huntington’s disease (HD) is a poster child of protein misfolding neurodegenerative disorders. The presence of neuronal inclusions of mutant huntingtin N-terminal fragments, mainly in the cortex and striatum, is a neuropathological hallmark of HD. Inhibition of protein misfolding and aggregation has been attempted using a variety of conventional protein stabilizers. Methods: This review describes how, in recent times, nucleic acid therapeutics has emerged as a selective tool to downregulate the aberrant transcript and reduce expression of mutant huntingtin, thereby alleviating protein aggregation. Different strategies of use of nucleic acids, including antisense oligonucleotides, short inhibitory RNA sequences and aptamers have been discussed. The following patent databases were consulted: European Patent Office (EPO), the United States Patent and Trademark Office (USPTO), Patent scope Search International and National Patent Collections (WIPO) and Google Patents. Results: Tools such as RNA interference (RNAi) and antisense oligonucleotides (ASOs) are potential therapeutic agents which target the post-transcriptional step, accelerating mRNA degradation and inhibiting the production of the mutant protein. These nucleic acid sequences not only target the elongated CAG triplet repeat translating to an expanded polyglutamine tract in the mutant protein, but have also been used to target single nucleotide polymorphisms associated with the mutant allele. The therapeutic sequences have been investigated in a number of cells and animal models of HD. One antisense sequence, with desirable safety properties, has recently shown downregulation of huntingtin protein in a limited clinical trial. RNA aptamers have also shown promising results in inhibiting protein aggregation in a yeast model of HD. Novel drug delivery techniques have been employed to overcome the blood brain barrier for the use of these therapeutic sequences. Conclusion: The selectivity and specificity imparted by nucleic acids, along with novel delivery techniques, make them hopeful candidates for the development of a curative strategy for HD.

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David A., Putnam. "Antisense strategies and therapeutic applications". American Journal of Health-System Pharmacy 53, n. 2 (15 gennaio 1996): 151–60. http://dx.doi.org/10.1093/ajhp/53.2.151.

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The concepts underlying the antisense approach to disease therapy are discussed, and potential applications are examined. Antisense therapeutic agents bind to DNA or RNA sequences, biocking the synthesis of cellular proteins with unparalleled specificity. Transcription and translation are the two processes with which the agents interfere. There are three major classes of antisense agents: antisense sequences, commonly called antisense oligonucleotides; antigene sequences; and ribozymes. Antisense sequences are derivatives of nucleic acids that hybridize cytosolic messenger RNA (mRNA) sense strands through hydrogen bonding to complementary nucleic acid bases. Antigene sequences hybridize double-stranded DNA in the nucleus, forming triple helixes. Ribozymes, rather than inhibiting protein synthesis simply by binding to a single targeted mRNA. combine enzymatic processes with the specificity of antisense Iwse pairing, creating a molecule that can incapacitate multiple targeted niRNAs. Anti-sense therapeutic agents are being investigated in vitro and in vivo for use in treating human immunodeficiency virus infection, hepatitis B virus infection, herpes simplex virus infection, papillomavirus infection, cancer, restenosis, rheumatoid arthritis, and allergic disorders. Although many results are preliminary, some are promising and has e led to clinical trials. A major goal in developing methods of delivering antisense agents is to reduce their susceptibility to nucleases while retaining their ability to bind to targeted sites. Modification of the phosphodiester linkages in oligonucleotides can lend the sequences enzymatic stability without affecting their binding capacities. Carrier systems designed to protect the antisense structure and improve passage through the cell membrane include liposomes, water-soluble polyrners, and nanoparticles. The pharmacokinetics of anti-sense agents are under investigation. Antisense therapeutic agents have the potential to become an integral part of medicinal regimens.

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