The 2'-position of the carbohydrate moiety has proven to be a fertile position for oligonucleotide modifications for antisense technology. The 2'-modifications exhibit high binding affinity to target RNA, enhanced chemical stability and nuclease resistance and increased lipophilicity. All high binding affinity 2'-modifications have C3'-endo sugar pucker. In addition to gauche effects, charge effects are also important in determining the level of their nuclease resistance. Pharmacokinetic properties of oligonucleotides are altered by 2'-conjugates. For certain modifications (e.g., 2'-F), the configuration at the 2'-position, arabino vs. ribo, determines their ability to activate the enzyme RNase H.