Solid-phase supports for oligonucleotide synthesis.

This unit attempts to provide a reasonably complete inventory of over 280 solid supports available to oligonucleotide chemists for preparation of natural and 3'-modified oligonucleotides. Emphasis is placed on non-nucleosidic solid supports. The relationship between the structural features of linkers and their behavior in oligonucleotide synthesis and deprotection is discussed wherever the relevant observations are available.

Attachment of nucleosides and other linkers to solid-phase supports for oligonucleotide synthesis.

Specific step-by-step instructions for conversion of 5'-O-(4,4'-dimethoxytrityl)- and base-protected nucleosides and other mono-O-(4,4'-dimethoxytrityl)-protected diols to their hemisuccinate esters and their coupling to CPG (controlled-pore glass) supports bearing aminopropyl or long chain aminoalkyl groups are presented. Additional guidelines are provided for selecting a coupling protocol and performing in-process control.

Widespread suppression of huntingtin with convection-enhanced delivery of siRNA.

Huntington's disease is an autosomal dominant neurodegenerative disease caused by a toxic gain of function mutation in the huntingtin gene (Htt). Silencing of Htt with RNA interference using direct CNS delivery in rodent models of Huntington's disease has been shown to reduce pathology and promote neuronal recovery. A key translational step for this approach is extension to the larger non-human primate brain, achieving sufficient distribution of small interfering RNA targeting Htt (siHtt) and levels of Htt suppression that may have therapeutic benefit.

A conformationally preorganized universal solid support for efficient oligonucleotide synthesis.

A novel, conformationally preorganized nonnucleosidic universal solid support for oligonucleotide synthesis was developed. The solid support featured two chemically equivalent hydroxy groups locked in syn-periplanar orientation and orthogonally protected with 4,4'-dimethoxytrityl and acetyl groups. The solid support was extensively tested in the preparation of oligonucleotides and their phosphorothioate analogues containing 2'-deoxy, 2'-O-methyl, and 2'-O-methoxyethylnucleoside residues at the 3'-terminus.

Selective phosphate protection: a novel synthesis of double-labeled oligonucleotides.

[structure: see text] A novel, selective labeling of oligonucleotides with two different reporter groups is described. The oligonucleotide is synthesized using a stable 2-(4-methoxybenzamido)ethyl protection for a selected internucleosidic thiophosphate (PS) and a labile 2-(N-isopropyl-4-methoxybenzamido)ethyl for the 3'-terminal PS and internucleosidic phosphates. The latter group and the base protection are removed, and the 3'-terminal PS is labeled.