Antiviral polynucleotide conjugates

DETAILED DESCRIPTION OF THE INVENTION The present invention provides polynucleotide conjugates characterized by the properties of ligand binding and enhanced stability.
In the present specification, the term "enhanced stability", unless otherwise stated, refers to the superior thermal stability of a polynucleotide conjugate relative to its unlinked counterpart, as measured using melting temperature (Tm) assays established in the art.
The term "ligand" is used herein with reference to agents that bind measurably, in the context of an assay appropriate for that measurement, to nucleic acid structures, principally double- stranded structures but also single-stranded structures.
The term ligand is thus intended to embrace such agents as proteins, including proteins that regulate genetic processes such as transcription and translation, as well as non-protein entities including but not limited to intercalating agents and nucleic acid binding antibiotics as well as other nucleic acids.
The term "ligand-binding" is thus used with reference to polynucleotide conjugates that adopt a structure that is bound measurably by a ligand against which the conjugate is targeted.
In providing duplexed structures of enhanced stability, the present invention permits the use of double-stranded polynucleotide structures in a wide variety of applications not previously possible as a result of prior stability problems.
Because the chemically linked duplexed structures of the present invention are substantially more stable than their unlinked counterparts under physiological conditions, for example, therapeutic applications for duplexed structures are now feasible.
In addition, it will be appreciated that the stability-enhancing effect of the chemical linker can be exploited to eliminate polynucleotide regions that are otherwise required to permit formation and maintenance of the desired duplexed structure in vitro and in vivo.
Further, the chemical linkers employed to form the present polynucleotide conjugates are substantially resistant to nuclease digestion, a contributing factor to the instability of unlinked polynucleotide fragments in vivo