Spatial control of in vivo CRISPR–Cas9 genome editing via nanomagnets

The potential of CRISPR–Cas9-based therapeutic genome editing is hampered by difficulties in the control of the in vivo activity of CRISPR–Cas9. To minimize any genotoxicity, precise activation of CRISPR–Cas9 in the target tissue is desirable. Here, we show that, by complexing magnetic nanoparticles (MNPs) with recombinant baculoviral vectors (BVs), CRISPR–Cas9-mediated genome editing can be activated locally in vivo via a magnetic field. BV was chosen for in vivo gene delivery because of its large loading capacity and its ability to locally overcome systemic inactivation by the complement system. We demonstrate that a locally applied magnetic field can enhance the cellular entry of MNP-BVs, thereby avoiding BV inactivation and causing a transient transgene expression in the target tissue. Because BVs are inactivated elsewhere, gene delivery and in vivo genome editing via MNP-BVs are tissue-specific.