Inhibiting gene expression with locked nucleic acids (LNAs) that target chromosomal DNA

Randall L. Beane, Rosalyn Ram, Sylvie Gabillet, Khalil Arar, Brett P. Monia, David R. Corey

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


Oligonucleotides containing locked nucleic acid bases (LNAs) have increased affinity for complementary DNA sequences. We hypothesized that enhanced affinity might allow LNAs to recognize chromosomal DNA inside human cells and inhibit gene expression. To test this hypothesis, we synthesized antigene LNAs (agLNAs) complementary to sequences within the promoters of progesterone receptor (PR) and androgen receptor (AR). We observed inhibition of AR and PR expression by agLNAs but not by analogous oligomers containing 2′-methoxyethyl bases or noncomplementary LNAs. Inhibition was dose dependent and exhibited IC50 values of < 10 nM. Efficient inhibition depended on the length of the agLNA, the location of LNA bases, the number of LNA substitutions, and the location of the target sequence within the targeted promoter. LNAs targeting sequences at or near transcription start sites yielded better inhibition than LNAs targeting transcription factor binding sites or an inverted repeat. These results demonstrate that agLNAs can recognize chromosomal target sequences and efficiently block gene expression. agLNAs could be used for gene silencing, as cellular probes for chromosome structure, and therapeutic applications.

Original languageEnglish (US)
Pages (from-to)7572-7580
Number of pages9
Issue number25
StatePublished - Jun 26 2007

ASJC Scopus subject areas

  • Biochemistry


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