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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Bibliographic Details
Published in:PloS one 2011-03, Vol.6 (3), p.e17981-e17981
Main Authors: Macadangdang, Benjamin, Zhang, Ning, Lund, Paul E, Marple, Andrew H, Okabe, Mitsunori, Gottesman, Michael M, Appella, Daniel H, Kimchi-Sarfaty, Chava
Format: Article
Language:English
Subjects:
Acids
Amino acids
Apoptosis
ATP Binding Cassette Transporter, Sub-Family B
ATP-Binding Cassette, Sub-Family B, Member 1 - physiology
Biology
Cancer
Cells, Cultured
Chemistry
Chemotherapy
Cytometry
Deoxyribonucleic acid
Diabetes
DNA
Drug resistance
Drug Resistance, Multiple
Flow cytometry
Gene expression
Gene sequencing
Gene Silencing
Gene therapy
Genes
Genetic engineering
In vitro methods and tests
Kidney diseases
Laboratories
Microbial drug resistance
Multidrug resistance
Multidrug resistant organisms
Neuroblastoma
Nucleic acids
Nucleocapsids
Peptide nucleic acids
Peptide Nucleic Acids - administration & dosage
Peptides
Polymerase chain reaction
Proteins
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - genetics
Simian virus 40
Simian virus 40 - physiology
Transcription, Genetic
Virion - physiology
Viruses
Western blotting
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0017981