Abstract
Low molecular weight (LMW) cationic polymers show safety profile and biocompatibility, but are hindered of limited efficacy in gene delivery. This protocol describes a zinc(II) coordinative strategy to transform common LMW cationic polymers to highly efficient and safe gene vehicles. LMW cationic polymers exhibit lower efficacy compared to their high molecular weight counterparts, largely attributed to weaker nucleic acid binding. From this point of view, zinc dipicolylamine (Zn-DPA) analogs showing high phosphate binding affinity are used to functionalize LMW cationic polymers to obtain higher DNA encapsulation. In addition, for the purpose of DNA release, a bioreducible disulfide bond is introduced between cationic polymers and Zn-DPA analogues, which can be cleaved by abundant glutathione in cytoplasm. The Zn coordination strategy dramatically enhances transfection efficacy of LMW cationic polymers across diverse cell types, including primary and stem cells.
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Liu, S., Guo, T. (2021). Bioreducible Zinc (II)-Coordinative Polyethylenimine with Low Molecular Weight for Robust Gene Delivery of Primary and Stem Cells. In: Tian, H., Chen, X. (eds) Gene Delivery. Biomaterial Engineering. Springer, Singapore. https://doi.org/10.1007/978-981-33-6198-0_20-1
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DOI: https://doi.org/10.1007/978-981-33-6198-0_20-1
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