Water-Soluble, Meso-Substituted Cationic Porphyrins—a Family of Compounds for Cellular Delivery of Oligonucleotides

The delivery of oligonucleotides to appropriate intracellular compartments is crucial to their development as tools in gene function studies and as therapeutics. Here, we report the characterization of meso-substituted cationic porphyrins as a large class of water-soluble reagents for oligonucleotide delivery. These porphyrins form non-covalent complexes with single-stranded oligonucleotides and deliver these molecules into the nuclei of cell lines in culture. The porphyrins protect oligonucleotides from nuclease degradation, and delivery is unaffected by the presence of serum. Delivery capacity is dependent on the charge ratio and concentration of the oligonucleotide and porphyrin used to form the complex, on the chemical substituents of the oligonucleotide and on the identity of the cationic porphyrin. This class of molecules provides a versatile set of water-soluble delivery reagents that could contribute to the development of oligonucleotide drugs.