A novel 2'-modification, 2'-O-[2-(methylthio)ethyl] or 2'-O-MTE, has been incorporated into oligonucleotides and evaluated for properties relevant to antisense activity. The results were compared with the previously characterized 2'-O-[2-(methoxy)ethyl] 2'-O-MOE modification. As expected, the 2'-O-MTE modified oligonucleotides exhibited improved binding to human serum albumin compared to the 2'...

Phosphodiester and phosphorothioate oligonucleotides in alpha and beta configurations directed against the initiation codon region of the HIV-1 rev gene were evaluated for their ability to inhibit HIV-1 replication in acutely and chronically infected human CEM cells. Encapsulation in antibody-targeted liposomes (immunoliposomes) permitted intracellular delivery and distinction between oligonucl...

Novel 2'-O,4'-C-ethylene nucleosides have been synthesized as building blocks for antisense and antigene oligonucleotides. 2'-O,4'-C-Ethylene-bridged nucleic acids (ENA) comprising 2'-O,4'-C-ethylene nucleosides have considerable affinity to complementary RNA and double-stranded DNA. Incorporation of 2'-O,4'-C-ethylene nucleosides into oligonucleotides dramatically increase their resistance aga...

A technique is described that allows the concurrent synthesis of homologous regions of separate oligonucleotides. The technique utilizes synthesis columns that are readily interconverted between single-chambered and dual-chambered. The regions of the oligonucleotides that differ are synthesized separately with single-chamber columns, and with the single molecules joined, the homologous regions ...

Features characteristic to rheumatoid joint destruction, including synovial overgrowth and bone resorption, are experimentally produced by augmenting c-fos gene expression. We tested here if arthritic joint destruction was inhibited upon inactivation of the c-fos/AP-1 signal by administering short double-stranded AP-1 DNA oligonucleotides into mice with collagen-induced arthritis to compete for...