Introduction

The invention relates to functionalized calixarene derivatives able to interact and bind non-covalently with peptide-nucleic acids (PNA) and to transport them inside cells. These compounds can be used as non-viral vectors for cellular transfection of PNA avoiding modifications to the structure of the latter.​

Technical features

In the field of gene therapy it can be very useful to have artificial oligonucleotides (AON) available rather than natural ones to achieve greater stability and resistance to degradation and greater coupling efficiency with the target nucleic acid. Among the most interesting and promising AONs are peptide-nucleic acids (PNAs) whose potential is however strongly limited by their poor ability to cross cell membranes. One of the most effective methods at the moment is to modify each PNA that one wishes to carry into the cell by functionalizing it with a polyarginine chain. The calixarene-based vectors that are proposed here instead allow the efficient delivery of PNAs without requiring any modification of their structure, by simple and rapid mixing, thanks to the establishment of non-covalent interactions that make the vector universal as it is suitable for any PNA you want to carry.

Possible Applications

• Transport of peptide nucleic acids (PNA) inside cells with the function of: antigen, anti mRNA and anti-miRNA;
• Gene therapy or gene editing.

Advantages

• High transfection efficiency associated with limited or negligible toxicity;​
• Ease of preparation and formulation of the material to be transfected;​
• Reproducibility and unequivocal identification of the vector structure;
• ​Effectiveness of action even in the absence of «helper lipids»;
• ​No modification is required chemistry of the substrate to be transported.