Abstract
The application of Peptide Nucleic Acids (PNAs), mimics of DNA lacking the sugar-phosphate backbone, for antisense/anti-gene therapy and gene editing is limited by their low uptake by cells. Currently, no simple and efficient delivery systems and methods are available to solve this open issue. One of the most promising approach is the modification of the PNA structure through the covalent linkage of poliarginine tails, but this means that every PNA intended to be internalized must be modified. Herein we report the results relative to the delivery ability of a macrocyclic multivalent tetraargininocalix[4]arene (1) used as non-covalent vector for anti-miR-221-3p PNAs. High delivery efficiency, low cytotoxicity, maintenance of the PNA biological activity and ease preparation of the transfection formulation, simply attained by mixing PNA and calixarene, candidate this vector as universal delivery system for this class of nucleic acid analogues.
Highlights
Peptide nucleic acids (PNAs) are DNA analogues in which the sugar-phosphate backbone is replaced by N-(2-aminoethyl)glycine units[1,2,3,4,5,6]
As alternative to the chemical modification, for Peptide Nucleic Acids (PNAs) delivery convenient is the use of carriers able to interact with the cargo in a non-covalent and reversible way
This strategy would allow in principle to make available a system effective with all native PNA sequences that are intended to be transported into cells
Summary
Peptide nucleic acids (PNAs) are DNA analogues in which the sugar-phosphate backbone is replaced by N-(2-aminoethyl)glycine units[1,2,3,4,5,6]. As alternative to the chemical modification, for PNA delivery convenient is the use of carriers able to interact with the cargo in a non-covalent and reversible way This strategy would allow in principle to make available a system effective with all native PNA sequences that are intended to be transported into cells. The exploited parallel arrangement of the amino acid units makes available, with respect to more classical polyarginine peptides, the primary α-amino groups that might favor the protection of the vector–DNA complex from the lysosomal degradation and facilitate the release of DNA from the endosomes into the cytosol through a proton sponge effect This would, in part, contribute to the high transfection efficiency observed in particular for argininocalix[4]arene 146 (Fig. 1)
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