*2.3.3.1 Peptide nucleic acid*

PNA is a synthetic DNA mimic in which the deoxyribose phosphate backbone is replaced by polyamide linkages [36] (**Figure 2c**). PNAs are biologically very stable and have good hybridization properties. However, they do not activate mRNA cleavage via RNase activity, but rather block translation and thus protein expression, by forming sequence-specific duplex with mRNA, hence generating steric hindrance. Due to their neutral backbone, PNAs have low solubility and their cellular uptake remains a challenge for exploiting them as therapeutics antisense. PNAs delivery can be enhanced annealing a PNA strand with a negatively charged complementary oligonucleotide, and then enclosed the obtained duplex with a cationic lipid. To this end, PNAs are also conjugated to peptides for improving their cellular uptake [37, 38]. Furthermore, PNA can elicit antigen effects by hybridizing with double-stranded DNA [36, 39] resulting in transcriptional arrest. Substantial data have revealed the effectiveness of PNA in gene silencing in various in vitro models [39, 40].
