Dicerna Pharmaceuticals, Inc.
Compositions comprising reversibly modified oligonucleotides and uses thereof

Abstract:

Disclosed herein are glutathione-sensitive oligonucleotides and methods of using the same. The glutathione-sensitive oligonucleotides may comprise at least one nucleotide represented by Formula I: ##STR00001## wherein A, B, I, J, L, R.sub.1, R.sub.2, R.sub.3, R.sub.4, U.sub.1, U.sub.2, W, and X are as defined in the specification. An illustrative glutathione-sensitive oligonucleotide of the disclosure may have the following chemical structure: ##STR00002## Any oligonucleotide of interest may be modified with a glutathione-sensitive moiety, including oligonucleotides used for in vivo delivery, such as nucleic acid inhibitor molecules. Also disclosed are glutathione-sensitive nucleotide and nucleoside monomers, including glutathione-sensitive nucleoside phosphoramidites that can be used, for example, in standard oligonucleotide synthesis methods. In addition, glutathione-sensitive nucleotide and nucleoside monomers without a phosphoramidite can be used therapeutically, for example, as anti-viral agents.