Targeting of Cancer-Related Proteins with PNA Oligomers

Margus Pooga; Ulo Langel

Abstract

Aberrant gene expression is characteristic to all cancer cells and pathophysiology in general. Selective inhibition of constitutively elevated expression of oncogenes provides an opportunity to hinder the proliferation of malignant cells. Small synthetic molecules that specifically interfere with transcription and/or translation have great potential as anticancer drugs. Currently first-generation antisense oligonucleotides are widely used to inhibit the oncogene expression. The second generation of antisense agents have been studied mainly in vitro. One of these agents, peptide nucleic acid (PNA) is an oligonucleotide mimic with a noncharged achiral polyamide backbone to which the nucleobases are linked. PNA oligomers bind tightly to complementary DNA or RNA and are very stable in biological fluids. PNA can inhibit transcription and translation of target genes by specifically hybridizing to DNA or mRNA. The in vitro experiments showing inhibition of target protein expression by PNA have been followed by the first successful applications of PNA as an antisense agent in cultured cells and also in vivo. Hopefully this will lead to a wider use of PNA in the studies of cancer biology and therapy.

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