Oligonucleotide constructs and uses thereof
Oligodeoxynucleotide-based immunostimulatory Toll-Like Receptor 9 (TLR9) agonists are described. Also described are compositions comprising the TLR9 agonists, methods of making the TLR9 agonists, and methods of using the TLR9 agonists to treat immune diseases, disorders or conditions, such as viral infections or cancer.
1. An ODN construct having the following structure:
5′ Toco-po(HEG)po(HEG)po-TpsCpoGpsTpsCpoGpsTpsTpsTpsTpsGpsTpsCpoGpsTpsTpsTpsTpsGpsTpsCpoGpsTpsT 3′ (SEQ ID NO: 27);
wherein:
Toco represents tocopherol;
HEG represents ((CH 2 ) 2 O) 6 ;
po represents a phosphodiester linkage; and
ps represents a phosphorothioate linkage,
wherein the tocopherol is covalently linked to the (HEG) directly via the po linkage, or indirectly via a second linker that is linked to (HEG) directly via the po linkage.
2. A pharmaceutical composition comprising the ODN construct of claim 1 and a pharmaceutically acceptable carrier.