LAUSR

ABSTRACT Introduction Gene delivery vectors are a crucial determinant for gene therapeutic efficacy. Usually, it is necessary to use an excess of cationic vectors to achieve better transfection efficiency. However, it will cause severe cytotoxicity. In addition, cationic vectors are not resistant to serum, suffering from reduced transfection efficiency by forming large aggregates. Therefore, there is an urgent need to develop optimized gene delivery vectors. Recently, fluorination of vectors has been extensively applied to increase the gene delivery performance because of the unique properties of both hydrophobicity and lipophobicity, and chemical and biological inertness. Areas covered This review will discuss the fluorophilic effects that impact gene delivery efficiency, and chemical modification approaches for fluorination. Next, recent advances and applications of fluorinated polymeric and lipidic vectors in gene therapy and gene editing are summarized. Expert opinion Fluorinated vectors are a promising candidate for gene delivery. However, it still needs further studies to obtain pure and well-defined fluorinated polymers, guarantee the biosafety, and clarify the detailed mechanism. Apart from the improvements in gene delivery, exploiting other versatility of fluorinated vectors, such as oxygen-carrying ability, high affinity with fluorine-containing drugs, and imaging property upon introducing 19 F, will further facilitate their applications in gene therapy.