γ-Amino Carboxylic Acid Modification Enhances the Efficacy of PNAs Targeting miR-221-3p in A549 Cells

Peptide nucleic acids (PNAs) are versatile tools for diagnostic and therapeutic applications, including gene regulation and miRNA targeting. However, their therapeutic potential is often limited by challenges such as biological efficacy. To address this, PNAs offer a key advantage over other nucleic acids--their ease of modification, which allows for enhanced properties. In this study, we introduced a novel{gamma} -amino carboxylic acid ({gamma}-ACA) modification to PNAs targeting miR-221-3p, a key miRNA implicated in various pathological processes. The modified PNAs showed significantly improved binding affinity to their targets and more efficient inhibition of miR-221-3p expression compared to unmodified PNAs in A549 cells, leading to effective regulation of downstream gene and protein expression. These results highlight the potential of{gamma} -modified PNAs as a platform for developing miRNA-targeted therapeutics.