title: Silencing of gene expression by gymnotic delivery of antisense oligonucleotides.
abstract: Antisense oligodeoxyribonucleotides have been used for decades to achieve sequence-specific silencing of gene expression. However, all early generation oligonucleotides (e.g., those with no other modifications than the phosphorothioate backbone) are inactive in vitro unless administered using a delivery vehicle. These delivery vehicles are usually lipidic but can also be polyamines or some other particulate reagent. We have found that by employing locked nucleic acid (LNA) phosphorothioate gap-mer nucleic acids of 16 mer or less in length, and by carefully controlling the plating conditions of the target cells and duration of the experiment, sequence-specific gene silencing can be achieved at low micromolar concentrations in vitro in the absence of any delivery vehicle. This process of naked oligonucleotide delivery to achieve gene silencing in vivo, which we have termed gymnosis, has been observed in many both adherent and nonadherent cell lines against several different targets genes.
authors: Department of Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, 111 East 210th Street, Hofheimer 1st Floor, Bronx, NY 10467, USA.
authors: Harris S
authors: HS
authors: Soifer
authors: Troels
authors: T
authors: Koch
authors: Johnathan
authors: J
authors: Lai
authors: Bo
authors: B
authors: Hansen
authors: Anja
authors: A
authors: Hoeg
authors: Henrik
authors: H
authors: Oerum
authors: C A
authors: CA
authors: Stein
mesh_terms: D001483:Base Sequence; D015153:Blotting, Western; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D015536:Down-Regulation; D055785:Gene Knockdown Techniques / Q000379:methods*; D020868:Gene Silencing; D006801:Humans; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics*; D009841:Oligonucleotides / Q000235:genetics; D011506:Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection / Q000379:methods
chemical_list: D020319:Oligodeoxyribonucleotides, Antisense; D009841:Oligonucleotides; D011506:Proteins; C477371:locked nucleic acid