Development of DNA Nanostructures for High-Affinity Binding to Human Serum Albumin

• DOI: 10.1021/jacs.7b02917
• Publication Date: 2017-05-05T16:46:57Z
• Authors: Aurélie Lacroix; Thomas G. W. Edwa...; Mark A. Hancock; Michael D. Dore; Hanadi F. Sleiman
• Keywords: Human serum albumin; Bovine serum albumin; Serum Albumin

The development of nucleic acid therapeutics has been hampered by issues associated with their stability and in vivo delivery. To address these challenges, we describe a new strategy to engineer DNA structures strong binding affinity human serum albumin (HSA). HSA is the most abundant protein blood long circulation half-life (19 days). It shown hinder phagocytosis, retained tumors, aids cellular penetration. Indeed, already successfully used for delivery small-molecule drugs nanoparticles. We show that conjugating dendritic alkyl chains creates amphiphiles exhibit high-affinity (Kd low nanomolar range) HSA. Notably, complexation did not activity silencing oligonucleotides inside cells, degradation strands was significantly slowed. also that, site-specific manner, altering number orientation amphiphilic ligand on self-assembled nanocube can modulate cage Moreover, amphiphile bound reach up 22 hours, whereas unconjugated single-stranded degraded within minutes. Therefore, adding protein-specific domains nanostructures be rationally control interface between synthetic biological systems. A major challenge nanoparticles quick formation corona (i.e., adsorbed nanoparticle surface) upon injection media. foresee such cage–protein complexes as tools study role this adsorption layer important implications efficient RNAi vitro vivo.