Covalently cross-linked oligonucleotides

DETAILED DESCRIPTION OF THE INVENTION In accordance with the objects of this invention novel, covalently cross-linked oligonucleotide strands are disclosed.
Preferably such strands are "duplexed" or "complementary" along at least a portion of their length.
In the context of this invention the terminology "duplex strands" or "complementary strands" or like terminology refers in a first instance to two separate strands wherein at least one nucleotide or nucleotide sequence on one of the strands is complementary to and specifically hybridizable with an opposing nucleotide or nucleotide sequence on the other strand.
In a second instance, this terminology refers to two sections or sequence regions of a single strand that are spaced from one another by a distance sufficient for the strand to fold onto itself and permit hybridization of complementary nucleotides in the respective sequence regions.
Folded, self-hybridizing, single strands form hairpin loop, stem loop, interior loop or bulge type structures as a result of such hybridization.
Further in the context of this invention, the term "oligonucleotide" refers to polynucleotides formed from a plurality of joined nucleotide units.
In certain instances, the nucleotides are formed from naturally occurring bases and pentofuranosyl sugars groups and are joined together via native inter-nucleoside phosphodiester linkages.
The term "oligonucleotide" thus effectively includes naturally occurring or synthetic species formed from naturally occurring subunits.
The term "oligonucleotide" also includes structures formed from modified or non-naturally occurring nucleotide subunits.
Modifications can occur on the base portion of a nucleotide, on a sugar portion,of a nucleotide or on the linkage joining one nucleotide to the next.
In addition, modifications can be made wherein nucleoside units are joined together with connecting groups that substitute for the inter-nucleoside phosphate linkages.
Inter-nucleoside connecting groups, which are to be distinguished from the cross-linkages of the invention, include --O--CH