An incredible amount of progress has been made for ex vivo genome editing; however, major challenges remain in the development of efficient, safe, and targetable in vivo delivery systems. To achieve high efficacy and safety in therapeutic in vivo genome editing, editing activities must be controlled spatially and temporally in the body, which requires novel materials, delivery strategies, and control mechanisms. To this end, our lab employs innovative, engineering approaches for viral vectors such as adeno-associated virus and baculovirus as well as non-viral vectors to achieve high delivery efficiency, tissue specificity, and safety for clinical translation.

The advancement of chemistry and synthetic biology has led to the generation of a large number of new therapeutic agents such as chemotherapy drugs and DNA that encodes genes. However, delivery of the therapeutic agents to the target sites represents a grand challenge. The Bao Lab has developed several magnetic nanoparticle-based strategies for targeted delivery of therapeutic agents. In one strategy, the magnetic nanoparticles are used to temporarily and locally increase the vascular permeability to facilitate targeted drug delivery. In another strategy, we developed a magnetic nanoparticle-baculovirus hybrid system for spatial control of CRISPR/Cas9 genome editing in vivo. In addition, we use the magnetic nanoparticles as drug carriers. The therapeutic drugs are loaded onto the magnetic nanoparticles via hydrophobic interaction or electrostatic interaction and delivered to the target tissue through external magnetic field. These targeted delivery approaches not only improve the therapeutic outcomes, but also reduce adverse side effects.