Lipid-DNA conjugates are amphiphilic macromolecules that combine the cell membrane insertion capability of lipids with the properties of DNA in terms of precise hybridization and programmability. Interestingly, by chemically conjugating hydrophobic lipid molecules and DNAs, several appealing features for cellular applications have been demonstrated, including (1) spontaneous, rapid, and efficient membrane insertion following simple incubation; (2) universality toward different cell types; and (3) versatile functionality due to simple DNA conjugation strategies. Different functional moieties can be efficiently engineered onto live cell membranes using lipid-DNA conjugates without affecting natural cellular behavior.
The preparation of lipid-DNA conjugates can be performed either before or after solid-phase DNA synthesis. In the pre-synthetic approach, lipid phosphoramidites are first synthesized and inserted into desired DNA sequences during solid-phase DNA synthesis. In the post-synthetic method, lipid moiety modification is achieved after the complete synthesis and purification of the DNA sequence. Our well-developed lipid-DNA conjugation strategies have paved the way for the emerging biological applications of lipid-DNA conjugates.