GLYCOSYLATED OLIGONUCLEOTIDES THAT MIMIC THE HIV-1 EPITOPE OF NEUTRALIZING MONOCLONAL ANTIBODY 2G12

摘要

Disclosed are oligonucleotides that binds specifically to HIV neutralizing monoclonal antibody 2G12 with a K₄ value lower than 20 nM, the oligonucleotide comprising a predicted structure, at 37° C., having exactly one stem-loop whereby the loop comprises the nucleotide sequence of AACCNACGGANAAA (SEQ ID NO: 1), where N is a modified nucleoside base, and the stem includes at least 3 nucleotide base-pairs and one of the nucleotides in the stem includes a modified nucleoside base, wherein the modified nucleoside base has the structure -B-L-A where A is a branched-chain Man₉ oligosaccharide, L is a linker molecule, and B is independently a pyrimidine or pyridine base linked to the sugar-phosphate backbone of the oligonucleotide. Immunogenic conjugates that include the oligonucleotide, and pharmaceutical compositions that include the oligonucleotide or the immunogenic conjugate are also disclosed. Various method of using the oligonucleotides, immunogenic conjugates, and pharmaceutical compositions are also disclosed.