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 drugs. Peptide nucleic acid (PNA), an oligonucleotide mimic, has a non-charged achiral polyamide backbone to which the nucleobases are attached. PNA oligomers are extremely stable in biological fluids and they specifically hybridise to DNA or RNA in a complementary manner, forming very strong heteroduplexes. Some of the mRNAs have yet undetermined and possibly long half-lives, successful down regulation of gene expression by antisense oligonucleotides (ON) requires that the antisense agent is long lived. PNA fulfils this requirement better than phosphodiester or phosphorothioate ONs. PNA can inhibit 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 application of PNA oligomers in vivo. This review discusses the principles of the in vitro and in vivo use of PNA oligonucleotides.
Pooga
M
M
Department of Neurochemistry and Neurotoxicology, Arrhenius Laboratories, Stockholm University, S-10691 Stockholm, Sweden.
Land
T
T
Bartfai
T
T
Langel
U
U
D000818:Animals; D001419:Bacteria / Q000187:drug effects / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000187:drug effects*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D018716:Molecular Mimicry; D009474:Neurons / Q000378:metabolism; D009692:Nucleic Acid Heteroduplexes; D016376:Oligonucleotides, Antisense / Q000737:chemistry* / Q000494:pharmacology; D020135:Peptide Nucleic Acids / Q000737:chemistry* / Q000494:pharmacology; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014779:Virus Replication
D009692:Nucleic Acid Heteroduplexes; D016376:Oligonucleotides, Antisense; D020135:Peptide Nucleic Acids; D012333:RNA, Messenger; D004247:DNA