Inhibiting Gene Expression with Locked Nucleic Acids (LNAs) That Target Chromosomal DNA

Autor: David R. Corey, Rosalyn Ram, Brett P. Monia, Sylvie Gabillet, Khalil Arar, Randall L. Beane
Rok vydání: 2007
Předmět:
Zdroj: Biochemistry. 46:7572-7580
ISSN: 1520-4995
0006-2960
DOI: 10.1021/bi700227g
Popis: 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
Databáze: OpenAIRE