The potential of clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR associated protein 9 (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 with recombinant baculoviral vectors (MNP-BVs), CRISPR–Cas9-mediated genome editing can be activated locally in vivo via a magnetic field. The baculoviral vector was chosen for in vivo gene delivery because of its large loading capacity and 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 baculoviral vector inactivation and causing a transient transgene expression in the target tissue. Because baculoviral vectors are inactivated elsewhere, gene delivery and in vivo genome editing via MNP-BVs are tissue specific.
|Number of pages||11|
|Journal||Nature Biomedical Engineering|
|State||Published - Feb 1 2019|
Bibliographical noteFunding Information:
We thank L. Volkman and T. Ohkawa for kindly providing the anti-vp39 antibody, and T. Davis, L. Hong and A. Ray for assistance. This work was supported by the National Institutes of Health through a Nanomedicine Development Center Award (PN2EY018244 to G.B.) and the Cancer Prevention and Research Institute of Texas (RR140081 and RR170721 to G.B.).
© 2018, The Author(s), under exclusive licence to Springer Nature Limited.
ASJC Scopus subject areas
- Medicine (miscellaneous)
- Biomedical Engineering
- Computer Science Applications