Light Activated, Inside-Out Nanoparticles Spatially Control CRISPR

Oligonucleotides complementary to the sgRNA of interest were attached to the surface of gold nanoparticles before annealing them to sgRNA:Cas9 ribonucleoprotein (RNP) complexes. Subsequently, when the particles were irradiated with near-infrared light, heat absorbed by the gold caused the annealed strands to dissociate from each other, thereby releasing the RNP.

The principle was first validated in vitro in brain cells, demonstrating virtually no gene editing without irradiation. Following near-infrared irradiation, however, gene editing occurred at the same high levels as using lipofectamine RNAiMAX delivery.

The inside-out nanoparticles were administered in vivo into the brains of mice, either by direct injection or intranasally. Following irradiation of only one hemisphere, gene editing was approximately 4-fold higher in the irradiated compared to the nonirradiated hemisphere.

The new gene-editing formulation for on-demand release into deep tissues with high-resolution spatial control upon exposure to transcranial NIR light may offer new possibilities for safely performing brain gene editing.

Susana Simões and Lino Ferreira led the study from the University of Coimbra, Portugal. It was published yesterday in Angewandte Chemie. You can read it here.