Evidence is presented that components of fetal calf serum (FCS) can significantly enhance the splicing correction activity of peptide nucleic acids (PNA) in HeLa pLuc 705 cells. The effect proved more pronounced for PNAs bearing fluorescence tags and relies on the ability of specific components of FCS to mediate a mainly nonendocytotic intracellular delivery of PNA. Attempts to isolate and characterize the active serum components using PNA-loaded beads and nano-LC-ESI mass spectrometry revealed the growth-factor related inter-alpha-trypsin inhibitor and the adhesion protein fibronectin to be substantially responsible for the delivery activity of FCS.

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