On Jan. 10, Cheng Yiyun, a professor of Shanghai Key Laboratory of Regulatory Biology and the School of Life Sciences, and his students published their latest discovery of the high gene transfection efficacy of fluorinated dendrimers in Nature Communication by the paper “A fluorinated dendrimer achieves excellent gene transfection efficacy at extremely low nitrogen to phosphorus ratios”.
Cheng Yiyun (R) and Wang Minming, a Ph.D candicate and a first co-author of the paper.
Gene therapy is the use of DNA as a drug to treat disease by delivering therapeutic DNA into a patient's cells. In gene therapy, DNA that encodes a therapeutic protein is packaged within a "vector", which is used to get the DNA inside cells within the body. Once inside, the DNA becomes expressed by the cell machinery, resulting in the production of therapeutic protein, which in turn treats the patient's disease. Since it was first conceptualized in 1972, gene therapy has been regarded as a promising treatment for patients. However, the widely clinic use of gene therapy still faces challenges, and what challenges the gene therapy treatment most is the lack of a vector with safety and high efficiency.
Cationic polymers are widely used as promising gene vectors to introduce exogenous nucleic acid into cells. These materials are easy-to-manufacture and have superior safety compared with viral gene vectors. However, their commercial and clinical applications are limited by relatively low transfection efficacy and poor cell viability after transfection. To solve the problem, Prof. Cheng Yiyun and his students tried to find a technique to achieve the high gene transfection efficacy of polymers.
Liu Hongmei, a Ph.D candicate and a first co-author of the paper, works in the lab.
In their research, they synthesize fluorinated dendrimers for use as gene vectors and find the dendrimers achieve excellent gene transfection efficacy in several cell lines (higher than 90% in HEK293 and HeLa cells) at extremely low N/P ratios. These polymers show superior efficacy and biocompatibility compared with several commercial transfection reagents such as Lipofectamine and SuperFect. Fluorination enhances the cellular uptake of the dendrimer/DNA polyplexes and facilitates their endosomal escape. In addition, the fluorinated dendrimer shows excellent serum resistance and exhibits high gene transfection efficacy even in medium containing 50% FBS. The results suggest that fluorinated dendrimers are a new class of highly efficient gene vectors and fluorination is a promising strategy to design gene vectors without involving sophisticated syntheses.
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Written by: Liu Jinyu