Effects in live cells of a c- myc anti-gene PNA linked to a nuclear localization signal

Peptide nucleic acids (PNA) are synthetic homologs of nucleic acids in which the phosphate-sugar polynucleotide backbone is replaced by a flexible polyamide. In this study, a PNA construct was employed as an anti-gene agent in intact cells in culture. The cell lines studied were derived from Burkitt's lymphomas (BL) that presented a translocated and hyperexpressed c- myc oncogene. A 17-mer anti- myc PNA, complementary to a unique sequence located at the beginning of the second exon of the oncogene, and was covalently linked at its N terminus to a nuclear localization signal (NLS) (PNA-myc wt -NLS). When BL cells were exposed to PNA-myc wt -NLS, the anti-gene construct was localized predominantly in the cell nuclei and a rapid consequent downregulation of c- myc expression occurred. Under these conditions, both completion of a productive cell cycle and apoptosis were inhibited.