Structural modifications toward improved antisense oligonucleotides

The medicinal chemistry effort directed toward improving antisense oligonucleotides has resulted in the synthesis of a large number of phosphate, ribose and heterocyclic base analogs. Most of the data published to date has evaluated modifications as to their effect on simple in vitro parameters, such as nuclease stability and melting temperature. From these analyses a number of analogs have emerged as candidates for further study. Currently, there are few well-controlled tissue culture and animal studies with which to evaluate these modifications and this is the challenge for the field of antisense oligonucleotides.