Figure 1.

Design and synthesis of lipid-oligonucleotide conjugates. (a) The conjugate typically comprises three moieties: lipid, linker, and nucleic acid. (b) Schematic of the pre-synthetic approach for the synthesis of lipid-oligonucleotide conjugates. Lipid phosphoramidite or lipid-conjugated controlled-pore glass (CPG) was conjugated together with other nucleotides during the solid-phase synthesis (SPS) of oligonucleotides. After cleavage from CPG, lipids were precisely modified at different positions of oligonucleotides. (c) Schematic of the post-synthetic approach for the synthesis of lipid-oligonucleotide conjugates. After solid-phase synthesis (SPS) of oligonucleotides containing some functional groups, lipids were then chemically conjugated through reaction with these functional groups.