Peptide nucleic acids, or PNAs, are oligonucleotide analogs in which the ph
osphodiester backbone is replaced with a polyamide structure. First synthes
ized less than 10 years ago, they have received great attention due to thei
r several favorable properties, including resistance to nuclease and protea
se digestion, stability in serum and cell extracts, and their high affinity
for RNA and single and double-stranded DNA targets. Although initially des
igned and demonstrated to function as antisense and antigene reagents that
inhibit both transcription and translation by steric hindrance, more recent
applications have included gene activation by synthetic promoter formation
and mutagenesis of chromosomal targets. Most notably for gene delivery, th
ey have been used to specifically label plasmids and act as adapters to lin
k synthetic peptides or ligands to the DNA. Thus, their great potential lie
s in the ability to attach specific targeting peptides to plasmids to circu
mvent such barriers to gene transfer as cell-targeting or nuclear localizat
ion, thereby increasing the efficacy of gene therapy. (C) 2000 Elsevier Sci
ence B.V. All rights reserved.