Cellular delivery of peptide nucleic acid (PNA).

Peptide nucleic acid (PNA) is a DNA mimic having a pseudopeptide backbone that makes it extremely stable in biological fluids. PNA binds complementary RNA and DNA with high affinity and specificity. These qualities make PNA a leading agent among "third generation" antisense and antigene agents. Unfortunately, fast progress in the exploration of PNA as an experimental and therapeutical regulator of gene expression has been hampered by the poor cellular uptake of PNA. However, a number of transfection protocols for PNA have now been established. These include microinjection, electroporation, co-transfection with DNA, conjugation to lipophilic moieties, conjugation to peptides, etc. Here we give a short introduction to the basic findings on PNA as an antisense and antigene agent in cell-free in vitro systems. This is followed by a comprehensive evaluation of the most interesting literature concerning cellular delivery and the intracellular effect of PNA. Also the current progress as regards using PNA as co-factor in DNA delivery is reviewed.