title: Antisense inhibitory effect: a comparison between 3'-partial and full phosphorothioate antisense oligonucleotides.
abstract: Phosphorothioate (PS) antisense oligonucleotides are currently used to inhibit many cell functions both in vivo and in vitro. However, these modified oligos provide reasonable sequence specificity only within a narrow concentration range. To overcome such a limitation we synthesized antisense oligomers, partially phosphorothioated, targeted against the human N-myc mRNA. We utilized such modified oligomers in a human neuroblastoma cell line where the N-myc gene expression was very high, and compared them to full phosphorothioate oligonucleotides. Both full PS and partial PS antisense oligos produced a maximum reduction in target mRNA after 6 h of treatment. They were able to maintain a good level of inhibition for 20 h only at high concentration. While partial PS oligos produced a dose dependent and sequence specific inhibition of N-myc mRNA, full PS molecules suffer from some disadvantages at the highest concentration used. Our results showed that partial PS molecules were capable of reducing gene expression showing a greater sequence specificity over a far broader concentration range. For this reason we conclude that partial PS antisense oligos, with respect to full PS antisense oligos, might be particularly useful for studying gene function.
authors.affiliation: Institute of Pharmacology and Toxicoogy, C.R.I.S.C.E.B, Second University of Naples, Italy. galderisi@yahoo.com
authors.forename: U
authors.initials: U
authors.lastname: Galderisi
authors.forename: G
authors.initials: G
authors.lastname: Di Bernardo
authors.forename: M A
authors.initials: MA
authors.lastname: Melone
authors.forename: G
authors.initials: G
authors.lastname: Galano
authors.forename: A
authors.initials: A
authors.lastname: Cascino
authors.forename: A
authors.initials: A
authors.lastname: Giordano
authors.forename: M
authors.initials: M
authors.lastname: Cipollaro
mesh_terms: D001483:Base Sequence; D001769:Blood; D017931:DNA Primers; D005786:Gene Expression Regulation / Q000187:drug effects; D016259:Genes, myc; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013873:Thionucleotides / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D017931:DNA Primers; D016376:Oligonucleotides, Antisense; D009943:Organophosphorus Compounds; D013873:Thionucleotides