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 whic h the phosphate-sugar polynucleotide backbone is replaced by a flexible pol yamide. In this study, a PNA construct was employed as an anti-gene agent i n intact cells in culture. The cell lines studied were derived from Burkitt 's lymphomas (BL) that presented a translocated and hyperexpressed c-myc on cogene. A 17-mer anti-myc PNA, complementary to a unique sequence located a t the beginning of the second exon of the oncogene, and was covalently link ed at its N terminus to a nuclear localization signal (NLS) (PNA-myc(wt)-NL S). 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 downr egulation of c-myc expression occurred. Under these conditions, both comple tion of a productive cell cycle and apoptosis were inhibited.