Therapeutic uses of peptide nucleic acids (PNA) in oncology

Peptide nucleic acids (PNAs) are DNA mimics in which the sugar-phosphate backbone has been replaced by an uncharged backbone based on amino acids. Due to their ability to bind to complementary polynucleotides, PNAs have been successfully used to inhibit transcription and/or translation of genes able to confer a survival advantage to cancer cells, such as c-myc and bcl-2. PNAs targeted to the RNA template region of telomerase have also been used to inhibit the catalytic activity of this enzyme, which is responsible for the immortalized phenotype of a large majority of tumor cells. Because it is thought that naked PNAs are not taken up spontaneously by most cells, a number of delivery strategies have been developed including the use of so-called 'cell-penetrating peptides'. Chimeric molecules made by coupling PNAs with such peptides have been shown to accumulate inside tumor cells to an extent sufficient to guarantee the biological effect of PNAs. Overall, these results indicate that PNAs may be useful tools for target-directed anticancer therapeutic interventions.