PNA oligomers as tools for specific modulation of gene expression

Small synthetic molecules that can specifically inhibit translation and/or transcription have shown great promise as potential antisense/antigene drug s. Peptide nucleic acid (PNA), an oligonucleotide mimic, has a non-charged achiral polyamide backbone to which the nucleobases are attached. PNA oligo mers are extremely stable in biological fluids and they specifically hybrid ise to DNA or RNA in a complementary manner, forming very strong heterodupl exes. Some of the mRNAs have yet undetermined and possibly long half-lives, successful down regulation of gene expression by antisense oligonucleotide s (ON) requires that the antisense agent is long lived. PNA fulfils this re quirement better than phosphodiester or phsphorothioate ONs. PNA can inhibi t transcription and translation of respective genes by tight binding to DNA or mRNA. First in vitro experiments to specifically down regulate protein expression by PNA have been followed by successful antisense and antigene a pplication of PNA oligomers in vivo. This review discusses the principles o f the in vitro and in vivo use of PNA oligonucleotides. (C) 2001 Elsevier S cience B.V. All rights reserved.