Biological activity of hexitol nucleic acids targeted at Ha-ras and intracellular adhesion molecule-1 mRNA

Citation
M. Vandermeeren et al., Biological activity of hexitol nucleic acids targeted at Ha-ras and intracellular adhesion molecule-1 mRNA, BIOCH PHARM, 59(6), 2000, pp. 655-663
Citations number
24
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
BIOCHEMICAL PHARMACOLOGY
ISSN journal
0006-2952 → ACNP
Volume
59
Issue
6
Year of publication
2000
Pages
655 - 663
Database
ISI
SICI code
0006-2952(20000315)59:6<655:BAOHNA>2.0.ZU;2-M
Abstract
Hexitol nucleic acid (HNA) is anew steric blocking oligonucleotide, hybridi zing sequence selectively with RNA. The biological activity of HNA was eval uated in an in vitro translation arrest system targeting Ha-ras mRNA and in a cellular system targeting intracellular adhesion molecule-1 (ICAM-1) exp ression. HNA very efficiently and selectively inhibited Ha-ras mRNA transla tion (IC50 Of 50 nM) when targeted at the translation initiation region. Wh en targeting at the 12th codon region, a gap-mer approach was needed to inh ibit mRNA translation. Similarly, I-INA inhibited ICAM-1 expression in kera tinocytes when targeting at codon sequences. In this test system, HNA is le ss active but more selective than phosphorothioates, but needs lipofection to become active in keratinocytes. This new steric blocker may be an effici ent antisense agent providing that enough material can be brought into cell s. (C) 2000 Elsevier Science Inc.