What are the benefits of using a 2'OMe/phosphorothioate chimera for antisense work?
Phosphorothioate bonds do tend to lead to non-specific effects because the sulfur can interact with proteins in the cell. 2'OMe avoids the non-specific binding and tends to bind tighter to its target. Mixing the two can increase the lifespan of the oligo in the cell. By limiting the number of thioate bonds to three, you can get the increased lifetime in the cell and limit some of the non-specific effects. There is a very good review on antisense modifications, their advantages and drawbacks, in the following journal: Kurreck, J. (2003) Eur. J. Biochem 270:1628-1644