CARB 1 |
| The successful development of oligonucleotides as therapeutics will undoubtedly require modification of the oligonucleotide sugar-phosphate backbone to enhance delivery, stability, efficacy and specificity. In fact, progress toward routine use in the clinic, especially for AON and siRNA therapy, has been slow, partly due to limitations in the currently available chemical modifications. Much recent work in one of our laboratories has focused on 2'-deoxy-2'-fluoroarabinonucleic acids (2'F-ANA), an AON modification expected to reach the clinic in 2008. Recent work has focused on 2'F-ANA modified siRNA and aptamers, which exhibit increases in nuclease stability with little loss of activity. As part of our ongoing program to develop 2'F-ANA modified oligonucleotides to target cellular RNA in vivo, we are exploring AON and siRNA containing 2'F-ANA and other functionalities (e.g., nucleosides, lipids, esters, and several other hydrophobic moieties) that may enhance their delivery and RNA silencing activity. Novel and efficient chemical methods for appending these modifications have been developed. In addition, positional effects of these modifications were explored, and in some cases synergy with 2'F-ANA, which has been previously established as a functional AON and siRNA modification, has been demonstrated. American Chemical Society Conference, New Orleans, April 6-10, 2008. |
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RNA as a Drug Target
8:20 AM-1:20 PM, Sunday, April 6, 2008 Morial Convention Center -- Rm. 214, Oral
Division of Carbohydrate Chemistry |