PLoS ONE (Mar 2011)

Inhibition of multidrug resistance by SV40 pseudovirion delivery of an antigene peptide nucleic acid (PNA) in cultured cells.

  • Benjamin Macadangdang,
  • Ning Zhang,
  • Paul E Lund,
  • Andrew H Marple,
  • Mitsunori Okabe,
  • Michael M Gottesman,
  • Daniel H Appella,
  • Chava Kimchi-Sarfaty

DOI
https://doi.org/10.1371/journal.pone.0017981
Journal volume & issue
Vol. 6, no. 3
p. e17981

Abstract

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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.