Non-biological gene carriers designed for overcoming the major extra- and intracellular hurdles in gene delivery, an updated review

Gene therapy as a modern therapeutic approach has not yet advanced to a globally-approved therapeutic approach. Lack of adequate reliable gene delivery system seems to be one of the major reasons from the pharmaceutical biotechnology point of view. Main obstacles delaying successful application of human gene therapy are presented in this review. The unique advantages of non-biological gene carriers as compared to their biological counterparts make them ideal alternatives for overcoming extra- and intracellular barriers in a more safely manner. We, therefore, highlight the significant contributions in non-biological gene delivery and favorable characteristics of different design attitudes with focus on in vivo approaches. Bypassing the rapid extracellular enzymatic degradation of genetic materials is covered in extracellular segment of this review with emphasis on PEGylated and targeted formulations. The successful approaches to pave the rest of the way from cellular uptake to intracellular transfer and gene expression of unpacked DNA are also discussed. From these approaches, we emphasize more on optimization of cationic-based polymers and dendrimers, developing newly designed membrane-effective components, and adjusting the hydrophilic-hydrophobic balance of the synthesized vectors

Gene transfer enhancement by alkylcarboxylation of poly[propylenimine]

Among synthetic carriers, dendrimers with the more flexible structure have attracted a great deal of researchers' attention in the field of gene delivery. Followed by the promising results upon hydrophobic modification on polymeric structures in our laboratory, alkylated poly [propylenimine]-based carriers were synthesized by nucleophilic substitution of amines with alkyl moieties and were further characterized for their physicochemical and biological characteristics for plasmid DNA delivery. Although not noticeably effective gene transfer activity for hexanoate- and hexadecanoate- modified series was observed, but alkylation by decanoic acid significantly improved the transfection efficiency of the final constructs up to 60 fold in comparison with unmodified poly[propylenimine] [PPI]. PPI modified by 10-bromodecanoic acid at 50% grafting, showed significantly higher gene expression at c/p ratio of 2 compared to Superfect as positive control. Overall, modification of PPI with 50% primary amines grafting with 10-bromodecanoic acid could increase the transfection efficiency which is occurred at lower c/p ratio when compared to Superfect, i.e. less amount of modified vector is required to exhibit the same efficiency as Superfect. Therefore, the obtained constructs seem to be safer carriers for long-term gene therapy applications