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: Benjamin Macadangdang, Ning Zhang, Paul E Lund, Andrew H Marple, Mitsunori Okabe, Michael M Gottesman, Daniel H Appella, Chava Kimchi-Sarfaty
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-03-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3062552?pdf=render
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author Benjamin Macadangdang
Ning Zhang
Paul E Lund
Andrew H Marple
Mitsunori Okabe
Michael M Gottesman
Daniel H Appella
Chava Kimchi-Sarfaty
author_facet Benjamin Macadangdang
Ning Zhang
Paul E Lund
Andrew H Marple
Mitsunori Okabe
Michael M Gottesman
Daniel H Appella
Chava Kimchi-Sarfaty
author_sort Benjamin Macadangdang
collection DOAJ
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.
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spelling doaj.art-dd7c724cc74243beaf6fc1084a3a33552022-12-21T19:40:29ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-03-0163e1798110.1371/journal.pone.0017981Inhibition of multidrug resistance by SV40 pseudovirion delivery of an antigene peptide nucleic acid (PNA) in cultured cells.Benjamin MacadangdangNing ZhangPaul E LundAndrew H MarpleMitsunori OkabeMichael M GottesmanDaniel H AppellaChava Kimchi-SarfatyPeptide 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.http://europepmc.org/articles/PMC3062552?pdf=render
spellingShingle Benjamin Macadangdang
Ning Zhang
Paul E Lund
Andrew H Marple
Mitsunori Okabe
Michael M Gottesman
Daniel H Appella
Chava Kimchi-Sarfaty
Inhibition of multidrug resistance by SV40 pseudovirion delivery of an antigene peptide nucleic acid (PNA) in cultured cells.
PLoS ONE
title 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_short 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
url http://europepmc.org/articles/PMC3062552?pdf=render
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