Antisense properties of peptide nucleic acids.
PNA is a nucleic acid analog with an achiral polyamide backbone consisting of N-(2-aminoethyl)glycine units (figure 1). The purine or pyrimidine bases are linked to the each unit via a methylene carbonyl linker (1-3) to target the complementary nucleic acid (4). PNA binds to complementary RNA or DNA in a parallel or antiparallel orientation following the Watson-Crick base-pairing rules (5-7). The uncharged nature of the PNA oligomers enhances the stability of the hybrid PNA/DNA(RNA) duplexes as compared to the natural homoduplexes. The non-natural character of the PNA makes PNA oligomers highly resistant to protease and nuclease attacks (8). These properties of PNA oligomers suggest that they could potentially serve as efficient antisense or antigene reagents. Indeed, peptide nucleic acids have been applied to block protein expression on the transcriptional (9) and translational level (10,11), and microinjected PNA oligomers demonstrate a strong antisense effect in intact cells (12). However, contrary to the "normal" nucleic acid analogs, PNA oligomers are not efficiently delivered into the cytoplasm of the cell, and until recently this has hindered the application of PNA oligomers as antisense reagents. In this work we summarize some recent achievements on PNA antisense application, especially these concerned with whole cell or tissue delivery of the PNA.
Soomets
U
U
Department of Neurochemistry and Neurotoxicology, Arrhenius Laboratories, Stockholm University, S-10691 Stockholm, Sweden.
Hällbrink
M
M
Langel
U
U
D000818:Animals; D002352:Carrier Proteins / Q000493:pharmacokinetics; D016373:DNA, Antisense / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015316:Genetic Therapy / Q000379:methods*; D008081:Liposomes / Q000493:pharmacokinetics; D020135:Peptide Nucleic Acids / Q000493:pharmacokinetics* / Q000627:therapeutic use*
D002352:Carrier Proteins; D016373:DNA, Antisense; D008081:Liposomes; D020135:Peptide Nucleic Acids