Inhibition of Multidrug Resistance by SV40 Pseudovirion Delivery of an Antigene Peptide Nucleic Acid (PNA) in Cultured Cells
نویسندگان
چکیده
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.
منابع مشابه
Cellular Morphology and Immunologic Properties of Escherichia coli Treated With Antimicrobial Antisense Peptide Nucleic Acid
Background & Objectives: Antisense peptide nucleic acids (PNA) that target growth essential genes show potent bactericidal properties without cell lysis. We considered the possibility that whether PNA treatment influence the bacteria total nucleic acids content and apply approach to develop a new delivery system to Dendritic cells (DCs). DCs are the most potent antigen presenting cells in th...
متن کاملDelivery of cell-penetrating peptide-peptide nucleic acid conjugates by assembly on an oligonucleotide scaffold.
Delivery to intracellular target sites is still one of the main obstacles in the development of peptide nucleic acids (PNAs) as antisense-antigene therapeutics. Here, we designed a self-assembled oligonucleotide scaffold that included a central complementary region for self-assembly and lateral regions complementing the PNAs. Assembly of cell-penetrating peptide (CPP)-PNAs on the scaffold signi...
متن کاملSequence-Specific Nucleic Acid Damage by Peptide Nucleic Acid Conjugates That Can Be
Inhibition of gene expression is of great interest to explore gene function or for therapeutic applications. Oligonucleotides that interact with a specific RNA (antisense strategy) or DNA (antigene strategy) sequence are very attractive to disrupt gene expression. Structural modifications brought to the last generation of oligonucleotides like PNAs (peptide nucleic acids) have led to molecules ...
متن کاملSequence-Specific Nucleic Acid Damage by Peptide Nucleic Acid Conjugates That Can Be
Inhibition of gene expression is of great interest to explore gene function or for therapeutic applications. Oligonucleotides that interact with a specific RNA (antisense strategy) or DNA (antigene strategy) sequence are very attractive to disrupt gene expression. Structural modifications brought to the last generation of oligonucleotides like PNAs (peptide nucleic acids) have led to molecules ...
متن کاملAn introduction to peptide nucleic acid.
Peptide Nucleic Acid (PNA) is a powerful new biomolecular tool with a wide range of important applications. PNA mimics the behaviour of DNA and binds complementary nucleic acid strands. The unique chemical, physical and biological properties of PNA have been exploited to produce powerful biomolecular tools, antisense and antigene agents, molecular probes and biosensors.
متن کامل