There are various feasible ways to engineer aptamers with extended bioavailability (e.g., stability and binding affinity in complex environments), regulating ability,
and multi-functional properties. Substitution of 2’-Ome, Fluoro RNA for
nucleotides at 5’-end, 3’-end and internal positions of aptamer and bulk moiety conjugation such as PEG, fatty acid, etc. at 5’-end
of aptamer offer advantages in high serum stability from nucleases and long retention time from renal clearance.