A non-cationic nucleic acid nanogel for the delivery of the CRISPR/Cas9 gene editing tool

Herein, we report a non-cationic DNA-crosslinked nanogel for intracellular delivery of a Cas9 and single guide RNA (Cas9/sgRNA) complex. A DNA-grafted polycaprolactone brush (DNA-g-PCL) is first loaded with the Cas9/sgRNA complex and then crosslinked by DNA linkers via nucleic acid hybridization to form a nanosized hydrogel, in which the gene editing tools are embedded and protected inside. With compact architecture, the Cas9/sgRNA complex-containing nanogel exhibited excellent physiological stability against nuclease digestion and enhanced cellular uptake efficiency, making the delivery system a promising tool for target genome editing.