Research On Novel Polycationic Gene Vector Formed Of Low-molecular-weight Polyethyleneimine And Bisformaldehyde Imidazole

Gene therapy, i.e., the expression in cells of genetic material with therapeutic activity, holds great promise for the treatment of a wide range of both inherited and acquired diseases. The lack of delivery system becomes the only key obstacle for bringing DNA/siRNA to clinical therapy. The majority of clinical solutions suffer from lacking of a safe and efficient vector, in order to target and play its role, carries need to overcome a series of complex bio-barriers in the body, including extracellular barriers and cellular barriers. Gene delivery vectors include both viral vectors and non-viral vectors, viral vectors take advantage of the facile integration of the gene of interest into the host and high probability of its long-term expression but are plagued by safety concerns. Nonviral delivery systems have been proposed as a more promising alternatives to viral vectors because they avoid the inherent immunogenicity and production problems that are seen when viral systems are used. Polycation vectors are particularly attractive for non-viral genetherapy. In this paper, a biodegradable polyethylenimine(PEI)-based polymer: polyethylenimine imidazole-1, 4-imine was designed, synthesized and evaluated in terms of its ability to deliver nucleic acids.This polymer was formed from a non-toxic and low-gene trafficking small-molecular-weight PEI, PEI 800 Da, and a safety-known drug metabolite, bisformaldhyde benzene, through a pH-responsive linkage, an bis-imine bond conjugated with an benzene ring. This polymer could condense pDNA at a w/w ratio above 3 to form 150-200 nm polyplexes, which was consistent with the observation by transmission electron microscopy(TEM) and atomic force microscope(AFM), and Zeta potential was in the range of 5-20 mV. Moreover, the polyplexes could achieve efficient cellular uptake and luciferase gene silencing by transfection of pDNA in COS-7 cells and HepG2 cells with negligible cytotoxicity, and also perform well in siRNA transfection in SMMC-7721 cells. All the results suggest that poly(polyethyleniimine) imidazlole-4,5-imine offered a promising example to balance the transfection efficiency and toxicity of a synthetic delivery system of nucleic acid.