Functionalized Poly(beta-Amino Ester)s for development of next generation gene delivery vectors
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A key end goal of gene delivery research is to develop clinically relevant vectors that can be used to combat elusive diseases such as AIDS. Despite promising engineering strategies, efficiency and ultimately gene modulation efficacy of nonviral vectors have been hindered by numerous in vitro and in vivo barriers that have resulted in subviral performance. Here it presents the existing gene delivery barriers and summarize current vector-specific strategies to overcome said barriers. With the understanding of the barriers, a library of 91 poly(beta-amino esters) (PBAEs) were synthesized in a high-throughput synthetic route. The polymers were characterized by 1H-NMR spectra and GPC. The structurally diverse polymer library was used for the regeneration of a hybrid bio-synthetic vector that combines the capabilities of both bacterial and polymer components for targeted gene delivery to APCs. In order to selectively transfect the cells of interest, a coherent method consists of coupling a ligand that is recognized by a receptor expressed at the cell surface to the carrier. Therefore, a new library of mannosylated poly(beta-amino ester)s (Man-PBAEs)were synthesized. The library was chosen such that small changes in the backbones carbon atom could be evaluated. The library of polymers were characterized by 1H-NMR spectra and GPC which confirmed the attachment of mannose to the polymers and its molecular and polydispersity index (PDI) respectively. The application of these Man-PBAE as biodegradable vectors for delivery of plasmid DNAs was investigated. In overall these nanocomplexes demonstrated exceptional transfection efficiency compared to the commercially available reagents (jet-PEI and Fugene 6).