Journal articles: 'Antisense nucleic acids'

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Goodchild, John. "Antisense nucleic acids and proteins." Cell Biophysics 18, no. 3 (June 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, no. 12 (November 19, 2013): 681. http://dx.doi.org/10.1038/nrurol.2013.271.

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Penchovsky, Robert, Antoniya V. Georgieva, Vanya Dyakova, Martina Traykovska, and Nikolet Pavlova. "Antisense and Functional Nucleic Acids in Rational Drug Development." Antibiotics 13, no. 3 (February 27, 2024): 221. http://dx.doi.org/10.3390/antibiotics13030221.

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This review is focused on antisense and functional nucleic acid used for completely rational drug design and drug target assessment, aiming to reduce the time and money spent and increase the successful rate of drug development. Nucleic acids have unique properties that play two essential roles in drug development as drug targets and as drugs. Drug targets can be messenger, ribosomal, non-coding RNAs, ribozymes, riboswitches, and other RNAs. Furthermore, various antisense and functional nucleic acids can be valuable tools in drug discovery. Many mechanisms for RNA-based control of gene expression in both pro-and-eukaryotes and engineering approaches open new avenues for drug discovery with a critical role. This review discusses the design principles, applications, and prospects of antisense and functional nucleic acids in drug delivery and design. Such nucleic acids include antisense oligonucleotides, synthetic ribozymes, and siRNAs, which can be employed for rational antibacterial drug development that can be very efficient. An important feature of antisense and functional nucleic acids is the possibility of using rational design methods for drug development. This review aims to popularize these novel approaches to benefit the drug industry and patients.

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Soomets, Ursel. "Antisense properties of peptide nucleic acids." Frontiers in Bioscience 4, no. 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, no. 4 (1999): d782–786. http://dx.doi.org/10.2741/a394.

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Tonkinson, J. L., and C. A. Stein. "Antisense Nucleic Acids — Prospects for Antiviral Intervention." Antiviral Chemistry and Chemotherapy 4, no. 4 (August 1993): 193–200. http://dx.doi.org/10.1177/095632029300400401.

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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, and Satoshi Obika. "Biological applications of xeno nucleic acids." Molecular BioSystems 13, no. 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, no. 4 (November 1, 1992): 745–46. http://dx.doi.org/10.1042/bst0200745.

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Flores, Maria Vega C., David Atkins, Thomas Stanley Stewart, Arthur van Aerschot, and Piet Herdewijn. "Antimalarial antisense activity of hexitol nucleic acids." Parasitology Research 85, no. 10 (August 24, 1999): 864–66. http://dx.doi.org/10.1007/s004360050647.

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Nielsen, Peter. "Targeting structured nucleic acids with antisense agents ▾." Drug Discovery Today 8, no. 10 (May 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, no. 17 (April 9, 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, no. 1 (January 25, 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 (April 2021): 64–71. http://dx.doi.org/10.1016/j.thromres.2021.01.006.

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Burnham, Martin, and Yinduo Ji. "Antisense Peptide Nucleic Acids in Antibacterial Drug Discovery." Molecular Therapy 10, no. 4 (October 2004): 614–15. http://dx.doi.org/10.1016/j.ymthe.2004.09.005.

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15

Baulcombe, David. "Antisense nucleic acids and proteins: Fundamentals and applications." Trends in Genetics 9, no. 3 (March 1993): 94–95. http://dx.doi.org/10.1016/0168-9525(93)90232-7.

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16

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, no. 5087 (November 27, 1992): 1481–85. http://dx.doi.org/10.1126/science.1279811.

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Zimmer, Ch. "Antisense Nucleic Acids and Protein: Fundamentals and Applications." Journal of Electroanalytical Chemistry 342, no. 2 (April 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, no. 2 (April 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, and Jens Bo Hansen. "siRNA Versus Antisense Locked Nucleic Acids: Stay Single!." Blood 106, no. 11 (November 16, 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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Hélène, C. "Control of oncogene expression by antisense nucleic acids." European Journal of Cancer 30, no. 11 (January 1994): 1721–26. http://dx.doi.org/10.1016/0959-8049(93)e0352-q.

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Neidle, Stephen. "Antisense Nucleic Acids and Proteins: Fundamentals and Applications." International Journal of Biological Macromolecules 16, no. 2 (April 1994): 110. http://dx.doi.org/10.1016/0141-8130(94)90025-6.

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Levina, A. S., M. N. Repkova, and V. F. Zarytova. "Therapeutic Nucleic Acids against Herpes Simplex Viruses." Биоорганическая химия 49, no. 6 (November 1, 2023): 591–610. http://dx.doi.org/10.31857/s013234232306009x.

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The Herpes simplex virus (HSV) causes a wide range of diseases, ranging from relatively mild primary skin lesions to severe and often fatal episodes of encephalitis. Currently, the most effective drugs for HSV-infected people are nucleoside analogs (e.g., acyclovir) targeting enzymes encoded by viral DNA. The effectiveness of nucleoside analogs is reduced because of poor solubility in water, rapid intracellular catabolism, high cellular toxicity, and the appearance of resistant viral strains. Antisense technology that exploits nucleic acid fragments (NA-based agents) is a promising alternative to antiviral therapy due to the high affinity of these agents to target nucleic acids, their high solubility in water, and lower cellular toxicity. In the last decade, antisense oligonucleotides have been investigated as potential drugs for various diseases associated with “harmful” nucleic acids. Oligonucleotides with different chemical modifications targeted at specific regions of the HSV genome have shown effectiveness in suppressing the virus. siRNA-based agents have demonstrated prolonged and effective (up to 99%) inhibition of HSV replication. Based on the publications reviewed in the review over the past 30 years, it can be concluded about the prospects of using NA-based agents to combat herpes viral infections.

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

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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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Levina, Asya S., Marina N. Repkova, Oleg Y. Mazurkov, Elena V. Makarevich, Natalya A. Mazurkova, and Valentina F. Zarytova. "Nanocomposites consisting of titanium dioxide nanoparticles, antisense oligonucleotides, and photoactive groups as agents for effective action on nucleic acids." Journal of microbiology, epidemiology and immunobiology 101, no. 1 (March 13, 2024): 127–32. http://dx.doi.org/10.36233/0372-9311-456.

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Relevance. Studies on model systems have confirmed the effectiveness of antisense oligonucleotides, including those that contain photoactive groups, for the modification of nucleic acids. However, this strategy has not yet found wide application due to the lack of successful methods for the cellular delivery. The development of effective preparations capable of acting on target nucleic acids in cells is an urgent task. The objective of the work is to create nanocomposites consisting of TiO2 nanoparticles, antisense oligonucleotides, and photoactive groups and to study their effect on target nucleic acids by the example of inhibition of influenza A virus replication in the cellular system. Materials and methods. Influenza virus A/Aichi/2/68 (A/H3N2), N-succinimide ether of p-azidotetrafluorobenzoic acid, TiO2 nanoparticles, and oligodeoxyribonucleotides have been used in the work. The antiviral activity of the proposed nanocomposites has been studied on the MDCK cells infected with the A/H3N2 virus. Results and discussion. Unique nanocomposites have been created, which consist of three functional components, i.e., titanium dioxide nanoparticles, antisense oligonucleotides, and the photoactive tetrafluoroarylazide group, respectively, providing penetration into cells, selective interaction with target nucleic acids, and photomodification of the targets. A significant antiviral site-specific action of the nanocomposites has been demonstrated against the influenza A virus in the cellular system, which exceeds the effect of the analogous samples that contain no photoactive groups. Conclusion. The biological activity of the created nanocomposites has been demonstrated by the example of highly effective suppression of influenza A virus replication in the cellular system. The results indicate the prospects of using the proposed drugs to affect target nucleic acids inside cells.

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Jani, Saumya, Maria Soledad Ramirez, and Marcelo E. Tolmasky. "Silencing Antibiotic Resistance with Antisense Oligonucleotides." Biomedicines 9, no. 4 (April 12, 2021): 416. http://dx.doi.org/10.3390/biomedicines9040416.

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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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Perche, Federico, Tony Le Gall, Tristan Montier, Chantal Pichon, and Jean-Marc Malinge. "Cardiolipin-Based Lipopolyplex Platform for the Delivery of Diverse Nucleic Acids into Gram-Negative Bacteria." Pharmaceuticals 12, no. 2 (May 28, 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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Malik, Shipra, W. Mark Saltzman, and Raman Bahal. "Extracellular vesicles mediated exocytosis of antisense peptide nucleic acids." Molecular Therapy - Nucleic Acids 25 (September 2021): 302–15. http://dx.doi.org/10.1016/j.omtn.2021.07.018.

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Kurreck, J. "Design of antisense oligonucleotides stabilized by locked nucleic acids." Nucleic Acids Research 30, no. 9 (May 1, 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, no. 3 (March 2006): 99–101. http://dx.doi.org/10.1016/j.molmed.2006.01.004.

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Herdewijn, P. "Conformationally restricted carbohydrate-modified nucleic acids and antisense technology." Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression 1489, no. 1 (December 1999): 167–79. http://dx.doi.org/10.1016/s0167-4781(99)00152-9.

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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, no. 10 (May 9, 2000): 5633–38. http://dx.doi.org/10.1073/pnas.97.10.5633.

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Aerschot Van, Arthur, Ilse Verheggen, Chris Hendrix, and Piet Herdewijn. "1,5-Anhydrohexitol Nucleic Acids, a New Promising Antisense Construct." Angewandte Chemie International Edition in English 34, no. 12 (July 7, 1995): 1338–39. http://dx.doi.org/10.1002/anie.199513381.

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Le, Bao T., Vyacheslav V. Filichev, and 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, no. 97 (2016): 95169–72. http://dx.doi.org/10.1039/c6ra22346j.

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Traykovska, Martina, Sjoerd Miedema, and Robert Penchovsky. "Clinical Trials of Functional Nucleic Acids." International Journal of Biomedical and Clinical Engineering 7, no. 2 (July 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, no. 4 (November 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, and Yongjian Liu. "Antisense peptide nucleic acid-functionalized cationic nanocomplex for in vivo mRNA detection." Interface Focus 3, no. 3 (June 6, 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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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, no. 1 (January 2, 2021): 54–60. http://dx.doi.org/10.55453/rjmm.2021.124.1.7.

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"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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Nielsen, Peter E. "Peptide nucleic acids as antibacterial agents via the antisense principle." Expert Opinion on Investigational Drugs 10, no. 2 (February 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, and P. Herdewijn. "Methylated Hexitol Nucleic Acids, Towards Congeners with Improved Antisense Potential." Nucleosides, Nucleotides and Nucleic Acids 22, no. 5-8 (October 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, and Luisa Tondelli. "Comparison of novel delivery systems for antisense peptide nucleic acids." Journal of Controlled Release 109, no. 1-3 (December 2005): 24–36. http://dx.doi.org/10.1016/j.jconrel.2005.09.013.

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Fattal, Elias, and Amélie Bochot. "Ocular delivery of nucleic acids: antisense oligonucleotides, aptamers and siRNA." Advanced Drug Delivery Reviews 58, no. 11 (November 2006): 1203–23. http://dx.doi.org/10.1016/j.addr.2006.07.020.

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Lee, Hyung Tae, Se Kye Kim, and Jang Won Yoon. "Antisense peptide nucleic acids as a potential anti-infective agent." Journal of Microbiology 57, no. 6 (May 27, 2019): 423–30. http://dx.doi.org/10.1007/s12275-019-8635-4.

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Yamamoto, Tsuyoshi, Aiko Yahara, Reiko Waki, Hidenori Yasuhara, Fumito Wada, Mariko Harada-Shiba, and Satoshi Obika. "Amido-bridged nucleic acids with small hydrophobic residues enhance hepatic tropism of antisense oligonucleotides in vivo." Organic & Biomolecular Chemistry 13, no. 12 (2015): 3757–65. http://dx.doi.org/10.1039/c5ob00242g.

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Abt, Corina, Lisa Marie Gerlach, Jana Bull, Anette Jacob, Bernd Kreikemeyer, and Nadja Patenge. "Pyrenebutyrate Enhances the Antibacterial Effect of Peptide-Coupled Antisense Peptide Nucleic Acids in Streptococcus pyogenes." Microorganisms 11, no. 9 (August 22, 2023): 2131. http://dx.doi.org/10.3390/microorganisms11092131.

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Antisense peptide nucleic acids (PNAs) inhibit bacterial growth in several infection models. Since PNAs are not spontaneously taken up by bacteria, they are often conjugated to carriers such as cell-penetrating peptides (CPPs) in order to improve translocation. Hydrophobic counterions such as pyrenebutyrate (PyB) have been shown to facilitate translocation of peptides over natural and artificial membranes. In this study, the capability of PyB to support translocation of CPP-coupled antisense PNAs into bacteria was investigated in Streptococcus pyogenes and Streptococcus pneumoniae. PyB enhanced the antimicrobial activity of CPP-conjugated antisense PNAs in S. pyogenes. The most significant effect of PyB was observed in combination with K8-conjugated anti-gyrA PNAs. In contrast, no significant effect of PyB on the antimicrobial activity of CPP-conjugated PNAs in S. pneumoniae was detected. Uptake of K8-FITC into S. pyogenes, Escherichia coli, and Klebsiella pneumoniae could be improved by pre-incubation with PyB, indicating that PyB supports the antimicrobial effect of CPP-antisense PNAs in S. pyogenes by facilitating the translocation of peptides across the bacterial membrane.

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Mercurio, Silvia, Silvia Cauteruccio, Raoul Manenti, Simona Candiani, Giorgio Scarì, Emanuela Licandro, and Roberta Pennati. "Exploring miR-9 Involvement in Ciona intestinalis Neural Development Using Peptide Nucleic Acids." International Journal of Molecular Sciences 21, no. 6 (March 15, 2020): 2001. http://dx.doi.org/10.3390/ijms21062001.

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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, no. 2 (June 30, 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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Prajapati, Rama, and Álvaro Somoza. "Albumin Nanostructures for Nucleic Acid Delivery in Cancer: Current Trend, Emerging Issues, and Possible Solutions." Cancers 13, no. 14 (July 9, 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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Kurupati, Prathiba, Kevin Shyong Wei Tan, Gamini Kumarasinghe, and 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, no. 3 (December 11, 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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Zhang, Yumin, Jiang He, Guozheng Liu, Jean-Luc Venderheyden, Suresh Gupta, Mary Rusckowski, and Donald J. Hnatowich. "Initial observations of 99mTc labelled locked nucleic acids for antisense targeting." Nuclear Medicine Communications 25, no. 11 (November 2004): 1113–18. http://dx.doi.org/10.1097/00006231-200411000-00008.

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

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Journal articles on the topic 'Antisense nucleic acids'

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