A Kinetic Model of Oligonucleotide-Brush Interactions for the Rational Design of Gene Delivery Vectors.

A Kinetic Model of Oligonucleotide-Brush Interactions for the Rational Design of Gene Delivery Vectors. Biomacromolecules. 2019 Apr 24;: Authors: Qu F, Li D, Ma X, Chen F, Gautrot J Abstract Polymer brushes are attractive candidates for the design of gene delivery vectors as they allow the systematic study of the impact of structural (type, size and shape of nanomaterials core) and physico-chemical parameters (cationic monomer chemistry, brush thickness and grafting density) on transfection efficiency. However, relatively little is known of their interactions of oligonucleotides. To study such interactions, we use surface plasmon resonance and developed a kinetic model of brush binding and infiltration. We identify the striking impact that brush grafting density and thickness have on oligonucleotide kinetics of infiltration, binding affinity and maximum loading. Surprisingly, double stranded RNA molecules are found to load at significantly higher levels compared to DNA molecules of identical sequence (apart from uracils/thymines). Furthermore, analysis of the kinetics of adsorption of these oligonucleotides indicates that the stoichiometry of binding (the ration of amine vs. phosphate residues) is close to parity for the uptake of double stranded 20 bp RNA. Finally, nanoparticles were designed, to be used as gene transfection vectors and to quantify that the brush grafting density and thickness significantly impact transfection effic...
Source: Biomacromolecules - Category: Biochemistry Authors: Tags: Biomacromolecules Source Type: research