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      Peptide nucleic acids: Advanced tools for biomedical applications

      review-article
      a , * , b , c
      Journal of Biotechnology
      Elsevier B.V.
      PNA, Antigene, Antisense, Hybridization, PCR, Biosensor

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          Highlights

          • Peptide Nucleic Acids − DNA/RNA analogues.

          • Different Modifications on PNA backbone and their effects.

          • Neutral backbone − remarkable hybridization properties.

          • PNA based biosensors and their diverse biomedical applications.

          • Potential antigene and antisense agents.

          Abstract

          Peptide Nucleic Acids (PNAs) are the DNA/RNA analogues in which sugar-phosphate backbone is replaced by N-2-aminoethylglycine repeating units. PNA contains neutral backbone hence due to the absence of electrostatic repulsion, its hybridization shows remarkable stability towards complementary oligonucleotides. PNAs are highly resistant to cleavage by chemicals and enzymes due to the substrate specific nature of enzymes and therefore not degraded inside the cells. PNAs are emerging as new tools in the market due to their applications in antisense and antigene therapies by inhibiting translation and transcription respectively. Hence, several methods based on PNAs have been developed for designing various anticancer and antigene drugs, detection of mutations or modulation of PCR reactions. The duplex homopurine sequence of DNA may also be recognized by PNA, forming firm PNA/DNA/PNA triplex through strand invasion with a looped-out DNA strand. PNAs have also been found to replace DNA probes in varied investigative purposes. There are several disadvantages regarding cellular uptake of PNA, so modifications in PNA backbone or covalent coupling with cell penetrating peptides is necessary to improve its delivery inside the cells. In this review, hybridization properties along with potential applications of PNA in the field of diagnostics and pharmaceuticals are elaborated.

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          Most cited references119

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          PNA hybridizes to complementary oligonucleotides obeying the Watson-Crick hydrogen-bonding rules.

          DNA analogues are currently being intensely investigated owing to their potential as gene-targeted drugs. Furthermore, their properties and interaction with DNA and RNA could provide a better understanding of the structural features of natural DNA that determine its unique chemical, biological and genetic properties. We recently designed a DNA analogue, PNA, in which the backbone is structurally homomorphous with the deoxyribose backbone and consists of N-(2-aminoethyl)glycine units to which the nucleobases are attached. We showed that PNA oligomers containing solely thymine and cytosine can hybridize to complementary oligonucleotides, presumably by forming Watson-Crick-Hoogsteen (PNA)2-DNA triplexes, which are much more stable than the corresponding DNA-DNA duplexes, and bind to double-stranded DNA by strand displacement. We report here that PNA containing all four natural nucleobases hybridizes to complementary oligonucleotides obeying the Watson-Crick base-pairing rules, and thus is a true DNA mimic in terms of base-pair recognition.
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            Sequence-selective recognition of DNA by strand displacement with a thymine-substituted polyamide.

            A polyamide nucleic acid (PNA) was designed by detaching the deoxyribose phosphate backbone of DNA in a computer model and replacing it with an achiral polyamide backbone. On the basis of this model, oligomers consisting of thymine-linked aminoethylglycyl units were prepared. These oligomers recognize their complementary target in double-stranded DNA by strand displacement. The displacement is made possible by the extraordinarily high stability of the PNA-DNA hybrids. The results show that the backbone of DNA can be replaced by a polyamide, with the resulting oligomer retaining base-specific hybridization.
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              Nanoparticle-based therapy in an in vivo microRNA-155 (miR-155)-dependent mouse model of lymphoma.

              MicroRNA-155 (miR-155) is an oncogenic microRNA that regulates several pathways involved in cell division and immunoregulation. It is overexpressed in numerous cancers, is often correlated with poor prognosis, and is thus a key target for future therapies. In this work we show that overexpression of miR-155 in lymphoid tissues results in disseminated lymphoma characterized by a clonal, transplantable pre-B-cell population of neoplastic lymphocytes. Withdrawal of miR-155 in mice with established disease results in rapid regression of lymphadenopathy, in part because of apoptosis of the malignant lymphocytes, demonstrating that these tumors are dependent on miR-155 expression. We show that systemic delivery of antisense peptide nucleic acids encapsulated in unique polymer nanoparticles inhibits miR-155 and slows the growth of these "addicted" pre-B-cell tumors in vivo, suggesting a promising therapeutic option for lymphoma/leukemia.
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                Author and article information

                Contributors
                Journal
                J Biotechnol
                J. Biotechnol
                Journal of Biotechnology
                Elsevier B.V.
                0168-1656
                1873-4863
                29 July 2017
                10 October 2017
                29 July 2017
                : 259
                : 148-159
                Affiliations
                [a ]Department of Chemistry, School of Basic and Applied Sciences, Galgotias University, Greater Noida, U.P., India
                [b ]School of Vocational Studies & Applied Sciences, Gautam Buddha University, Greater Noida, U.P., India
                [c ]Department of Applied Science & Humanities, I.T.S Engineering College, Greater Noida, U.P., India
                Author notes
                [* ]Corresponding author. anjali21in@ 123456gmail.com
                Article
                S0168-1656(17)31551-1
                10.1016/j.jbiotec.2017.07.026
                7114329
                28764969
                968d456d-fc4a-4e31-b517-42b2e4dcb945
                © 2017 Elsevier B.V. All rights reserved.

                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
                : 11 March 2017
                : 23 May 2017
                : 23 July 2017
                Categories
                Article

                Biotechnology
                pna,antigene,antisense,hybridization,pcr,biosensor
                Biotechnology
                pna, antigene, antisense, hybridization, pcr, biosensor

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