Modified oligonucleotides containing both A-form conformation geometry and
B-from conformation geometry nucleotides are disclosed. The B-form
geometry allows the oligonucleotide to serve as substrates for RNase H
when bound to a target nucleic acid strand. The A-form geometry imparts
properties to the oligonucleotide that modulate binding affinity and
nuclease resistance. By utilizing C2' endo sugars or O4' endo sugars, the
B-form characteristics are imparted to a portion of the oligonucleotide.
The A-form characteristics are imparted via use of either 2'-O-modified
nucleotides that have 3' endo geometries or use of end caps having
particular nuclease stability or by use of both of these in conjunction
with each other.