Targeting of lentiviral vectors and positioning of transduced cells by magnetic nanoparticles and magnetic field

Magnetic nanoparticles (MNPs) are promising tools in regenerative medicine. Here, we combined targeting of lentiviral vectors (LVs) and positioning of transduced cells by magnetic nanoparticles and magnetic fields. We focused on the cardiovascular system and viral gene transfer under clinically relevant conditions.
Lentiviral vectors can efficiently transduce dividing and non-dividing cells and stably integrate their viral DNA into the host genome. Ex vivo gene transfer has to be adapted to the temperature (hypothermia) and time constraints defined by the need to preserve the organ. Through the formation of complexes of lentiviral vectors with MNPs local targeting of lentiviral vectors by magnetic forces can be achieved. In addition, targeting of viral vectors is a major challenge for in vivo gene delivery especially after intravascular application. Physical forces generated by blood flow impede on efficient gene transfer after intravascular administration.
Cell-based gene therapies rely on efficient positioning of genetically modified cells at specific sites within tissues and organs. Transduction with LV-MNP complexes renders the cells magnetic. Thereby, the MNP-loaded cells can be positioned by magnetic field application.

We were able to target LV/MNP transduced cells by applying magnetic fields even in perfused vessels ex vivo and in vivo. We tested positioning of endothelial cells transduced with magnetic lentiviral complexes in the context of a carotid injury model in vivo and observed re-endothelialization of parts of the commune carotid artery. To further optimize LV targeting, we tested a range of MNPs of the core-shell type with an iron oxide core diameter of about 10nm and different coatings in a variety of bioassays for different cell lines. Even cells that are hard to transduce by classical overnight transduction can efficiently infected by combination of LV/MNP complexes.

Funding/Competing Interests: No relevant conflicts of interest declared.