Highly Branched Poly(β-amino esters) for Non-Viral Gene Delivery: High Transfection Efficiency and Low Toxicity Achieved by Increasing Molecular Weight

Abstract

A successful polymeric gene delivery vector is denoted by both transfection efficiency and biocompatibility. However, the existing vectors with combined high efficacy and minimal toxicity still fall short. The most widely used polyethylene imine (PEI), polyamidoamine (PAMAM) and poly(dimethylaminoethyl methacrylate) (PDMAEMA) suffer from the correlation: either too toxic or little effective. Here, we demonstrate that with highly branched poly(β-amino esters) (HPAEs), a type of recently developed gene delivery vector, the high gene transfection efficiency and low cytotoxicity can be achieved simultaneously at high molecular weight (MW). The interactions of HPAE/DNA polyplexes with cell membrane account for the favorable correlation between molecular weight and biocompatibility. In addition to the effect of molecular weight, the molecular configuration of linear and branched segments in HPAEs is also pivotal to endow high transfection efficiency and low cytotoxicity. These findings provide renewed perspective for the further development of clinically viable gene delivery vectors.

Hydroxyl versus permethylated glycopolymers as gene carriers

“…Over recent years, significant efforts have been devoted to the synthesis of novel polymeric cationic vectors [1][2][3][4] that could become alternatives to viruses in gene therapy. Such alternatives aim to achieve high transfection efficiency, and overcome virus drawbacks, such as their potential immune responses in therapeutic settings or their high production costs [5].…”

Polymeric Amines and Ampholytes Derived from Poly(acryloyl chloride): Synthesis, Influence on Silicic Acid Condensation and Interaction with Nucleic Acid

“…Thus, synthesis of polymers for gene delivery is aimed on creation of structures showing a high buffer capacity in the neutral and slightly acidic range. Complex polymer structures containing high amounts of tertiary amine groups were recently obtained [45][46][47][48] and showed a high buffer capacity combined with enhanced transfection activity. Polymeric amines have been widely investigated as gene transfer agents [41,42].…”

Epidermolysis bullosa: Advances in research and treatment

“…Although non‐viral keratinocyte transfection is less efficient and, instead of nearly 100% viral transduction efficiency, reaches maximally 70% efficiency, it avoids the risk of insertional mutagenesis. Novel safer non‐viral transfer methods are currently being developed . Like replacement gene therapy, the majority of the current gene editing approaches aim for ex vivo therapy often including a selection step before grafting of corrected cells.…”