Journal of Vaccines & Vaccination

Optimization of nuclear-localization in a Multicomponent Non-viral Gene Delivery System

5^th Asia Pacific Global Summit and Expo on Vaccines & Vaccination

July 27-29, 2015 Brisbane, Australia

Wei Dai, Waleed M Hussein Peter M. Moyle and Istvan Toth

Posters-Accepted Abstracts: J Vaccines Vaccin

Abstract:

Gene Therapy is a technique utilized to treat diseases caused by missing, defective or overexpressing genes. Although viral vectors transfect cells efficiently, risks associated with their use limit their clinical applications1,2. Nonviral delivery systems are safer, easier to manufacture, more versatile and cost effective3. Previously studied gene delivery systems can successfully get through the cell membrane and release into cytoplasm4. However, the translocation onto the nuclear membrane and enter into the nucleus become a major challenge for gene delivery. In the current research, a library of multicomponent gnonviral gene delivery system incorporating a cationic Dendron (DEN), a cell penetrating peptide (TAT), an endosomal-disrupting peptide (GALA) and nuclear localization species (NLS) were produced (Figure 1). Four NLSs (SV40 T-antigen, nucleoplasmin, Dexamethasone and Retinoic acid) were selected to identify which one has the most efficient nuclear localization activity, and therefore is the best optimize gene delivery system. Peptide based components were synthesized by standard solid phase peptide synthesis, and GALA was conjugated to the system by ?click chemistry?. After finishing synthesis, these four different delivery systems will be tested and compared for DNA condensation ability, cellular uptake, and transfection efficiency. Delivery system without NLSs will be used as a negative control in the biological experiments Figure 1: Schematic presentation of multicomponent non-viral gene delivery system construct