Biodegradable Efficient Gene Vectors Constructed Based On Poly(Aspartic Acid)

Gene therapy has attracted intense research interest as an effective way to cure cancer and genetic disorders. However, the design of gene delivery vectors with low cytotoxicity and high transfection efficiency remains a great challenge. Non-viral vectors as the major type of gene delivery vectors exhibit advantages of noninfectious, no carrier capacity constraints, wide variety of sources, controlled chemical structure, large-scale production and low cytotoxicity and host immunogenicity. Poly (aspartic acid) had been widely used in biomedical field since they are non-toxic, biocompatible, and biodegradable. In the work, a series of PAsp-based biodegradable efficient gene vectors were functionalized via aminolysis reaction by low-molecular-weight PDMAEMA with one terminal primary amine group and other small molecules like diethyltriamine.The main work is summarized as follows:(1) A series of linear or star-shaped PAsp-based gene vectors were prepared via ring-opining polymerization of β-benzyl-L-aspartate N-carboxy anhydride (BLA-NCA) initiated by ethylenediamine (ED) or ED-functionalized CD cores, followed by functionalization via aminolysis reaction with low-molecular-weight PDMAEMA and ethylenediamine or ethanolamine (EA). Such different types of PAsp-based carriers were investigated in detail through a series of experiments including degradability, DNA binding capability, cytotoxicity, and gene transfection ability.(2) A series of linear or star-shaped (with different cores) PBLA (Poly (β-benzyl-L-aspartate)) were prepared via ring-opining polymerization of β-benzyl-L-aspartate N-carboxy anhydride (BLA-NCA) initiated by ethylenediamine (ED) or ED-functionalized CD cores (include a-CD and P-CD). Some phenyl were replaced by ethanolamine, the other reacted with CD cores of star-shaped PAsp functionalized by diethyltriamine via self assembly to prepare supramolecular gene vectors. Such different types of supramolecular gene vectors were investigated in detail through a series of experiments including DNA binding capability, cytotoxicity, and gene transfection ability.