UC Berkeley

The clinical application of non-viral vector-based gene transfer has been hampered by less efficiency, short-term transgene expression and toxicity. Polylipid nanoparticles we have developed have been demonstrated to be highly efficient and non-toxic. The duration of effective transgene expression is long enough for a particular target window in liver disorders, such as drug toxicity, alcoholic liver injury and ischemia/reperfusion-associated donor organ damage. Moreover, a high DNA-packaging capacity, an extremely low binding rate to serum proteins, and amendable synthetic approaches for a large quantity of production confer this formulation of lipid-based transfer of antioxidant genes a great potential of clinical application. This chapter covers our experience in the synthesis, formulation, optimization and validation of the polylipid nanoparticle-mediated antioxidantgene transfer for the development of liver-based gene delivery approaches tailored for particular clinical scenarios. We also share our efforts and challenges faced in moving this potential gene transfer approach towards clinical application.