Peptide nucleic acids: versatile tools for gene therapy strategies

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.