The Application Of Betaine Derivatives In Gene Carrier Material

Key hinderances to gene therapy remain the lack of safe, efficiency, and targeting capability. Synthetic gene-delivery agents generally do not possess high transfection efficiency while showing advantages in low toxicity, low immune response, robust capability for various genes and cost effectiveness. Recent results showed the excellent efficiency for gene delivery of polycarboxybetaine ester (pCB-ester) when mixed pCB-ester with quaternary and tertiary amine groups used. Effective endosomal escape, uncompromised packaging/unpackaging, and targeted delivery can be achieved with this hydrolyzable zwitterionic ester polymer-based gene delivery vectors. However, the pCB-ester with tertiary amine groups only, similar to the key groups in poly (ethylenimine) (PEI), showed very low transfection.To solve this puzzle, we investigated the DNA packing capability of pCB-ester with tertiary amine groups only, the toxicity, the surface charge density, the process of infection and endosome escape of the gene delivery vectors by this pCB-ester. Results indicated that the possible reason for low transfection efficiency comes from high hydrophobicity of pCB-ester. This assumption is supported by our preliminary results through modification the hydrophobicity of pCB-ester. Further investigation might reveal more important information in a fundamental understanding of the structure-property relationship for gene delivery to improve the efficiency of synthetic gene-delivery agents. After all, the pCB-ester with tertiary amine groups is still a valuable candidate for gene delivery.