Inhibition of Multidrug Resistance by SV40 Pseudovirion Delivery of an Antigene Peptide Nucleic Acid (PNA) in Cultured Cells

Peptide nucleic acid (PNA) is known to bind with extraordinarily high affinity and sequence-specificity to complementary nucleic acid sequences and can be used to suppress gene expression. However, effective delivery into cells is a major obstacle to the development of PNA for gene therapy applicati...

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Main Authors: Macadangdang, Benjamin, Zhang, Ning, Lund, Paul E., Marple, Andrew H., Okabe, Mitsunori, Gottesman, Michael M., Appella, Daniel H., Kimchi-Sarfaty, Chava
Format: Online
Language:English
Published: Public Library of Science 2011
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3062552/
id pubmed-3062552
recordtype oai_dc
spelling pubmed-30625522011-03-28 Inhibition of Multidrug Resistance by SV40 Pseudovirion Delivery of an Antigene Peptide Nucleic Acid (PNA) in Cultured Cells Macadangdang, Benjamin Zhang, Ning Lund, Paul E. Marple, Andrew H. Okabe, Mitsunori Gottesman, Michael M. Appella, Daniel H. Kimchi-Sarfaty, Chava Research Article Peptide nucleic acid (PNA) is known to bind with extraordinarily high affinity and sequence-specificity to complementary nucleic acid sequences and can be used to suppress gene expression. However, effective delivery into cells is a major obstacle to the development of PNA for gene therapy applications. Here, we present a novel method for the in vitro delivery of antigene PNA to cells. By using a nucleocapsid protein derived from Simian virus 40, we have been able to package PNA into pseudovirions, facilitating the delivery of the packaged PNA into cells. We demonstrate that this system can be used effectively to suppress gene expression associated with multidrug resistance in cancer cells, as shown by RT-PCR, flow cytometry, Western blotting, and cell viability under chemotherapy. The combination of PNA with the SV40-based delivery system is a method for suppressing a gene of interest that could be broadly applied to numerous targets. Public Library of Science 2011-03-22 /pmc/articles/PMC3062552/ /pubmed/21445346 http://dx.doi.org/10.1371/journal.pone.0017981 Text en This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Macadangdang, Benjamin
Zhang, Ning
Lund, Paul E.
Marple, Andrew H.
Okabe, Mitsunori
Gottesman, Michael M.
Appella, Daniel H.
Kimchi-Sarfaty, Chava
spellingShingle Macadangdang, Benjamin
Zhang, Ning
Lund, Paul E.
Marple, Andrew H.
Okabe, Mitsunori
Gottesman, Michael M.
Appella, Daniel H.
Kimchi-Sarfaty, Chava
Inhibition of Multidrug Resistance by SV40 Pseudovirion Delivery of an Antigene Peptide Nucleic Acid (PNA) in Cultured Cells
author_facet Macadangdang, Benjamin
Zhang, Ning
Lund, Paul E.
Marple, Andrew H.
Okabe, Mitsunori
Gottesman, Michael M.
Appella, Daniel H.
Kimchi-Sarfaty, Chava
author_sort Macadangdang, Benjamin
title Inhibition of Multidrug Resistance by SV40 Pseudovirion Delivery of an Antigene Peptide Nucleic Acid (PNA) in Cultured Cells
title_short Inhibition of Multidrug Resistance by SV40 Pseudovirion Delivery of an Antigene Peptide Nucleic Acid (PNA) in Cultured Cells
title_full Inhibition of Multidrug Resistance by SV40 Pseudovirion Delivery of an Antigene Peptide Nucleic Acid (PNA) in Cultured Cells
title_fullStr Inhibition of Multidrug Resistance by SV40 Pseudovirion Delivery of an Antigene Peptide Nucleic Acid (PNA) in Cultured Cells
title_full_unstemmed Inhibition of Multidrug Resistance by SV40 Pseudovirion Delivery of an Antigene Peptide Nucleic Acid (PNA) in Cultured Cells
title_sort inhibition of multidrug resistance by sv40 pseudovirion delivery of an antigene peptide nucleic acid (pna) in cultured cells
description Peptide nucleic acid (PNA) is known to bind with extraordinarily high affinity and sequence-specificity to complementary nucleic acid sequences and can be used to suppress gene expression. However, effective delivery into cells is a major obstacle to the development of PNA for gene therapy applications. Here, we present a novel method for the in vitro delivery of antigene PNA to cells. By using a nucleocapsid protein derived from Simian virus 40, we have been able to package PNA into pseudovirions, facilitating the delivery of the packaged PNA into cells. We demonstrate that this system can be used effectively to suppress gene expression associated with multidrug resistance in cancer cells, as shown by RT-PCR, flow cytometry, Western blotting, and cell viability under chemotherapy. The combination of PNA with the SV40-based delivery system is a method for suppressing a gene of interest that could be broadly applied to numerous targets.
publisher Public Library of Science
publishDate 2011
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3062552/
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