title: Inhibition of multidrug resistance by SV40 pseudovirion delivery of an antigene peptide nucleic acid (PNA) in cultured cells.
abstract: 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.
authors: Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
authors: Benjamin
authors: B
authors: Macadangdang
authors: Ning
authors: N
authors: Zhang
authors: Paul E
authors: PE
authors: Lund
authors: Andrew H
authors: AH
authors: Marple
authors: Mitsunori
authors: M
authors: Okabe
authors: Michael M
authors: MM
authors: Gottesman
authors: Daniel H
authors: DH
authors: Appella
authors: Chava
authors: C
authors: Kimchi-Sarfaty
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology; D002478:Cells, Cultured; D018432:Drug Resistance, Multiple; D020868:Gene Silencing; D020135:Peptide Nucleic Acids / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013539:Simian virus 40 / Q000502:physiology*; D014158:Transcription, Genetic; D014771:Virion / Q000502:physiology*
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D020135:Peptide Nucleic Acids; D012333:RNA, Messenger