In order for gene therapy to reach its full potential, several advances in the method of delivery are required. Perhaps most critical is the development of a safe and efficient vector that can overcome the limitations posed by current viral and non-viral systems. Whilst viral vectors provide high transfection efficiencies, they are limited by an inherent immunogenicity and high costs associated with large scale manufacture. On the other hand non-viral vectors, such as polyplexes and lipoplexes, offer a reduction in toxicity but are limited by their transfection efficiencies. Poly(ethylenimine) is the most widely used polymer for gene transfection. The high density of protonatable amines offers much improved transfection efficiencies, but its use is hindered by poor water solubility and a high toxicity.<br/>Previous work has shown that partial hydrolysis of poly(2-alkyl-2-oxazoline)s to yield poly[(2-alkyl-2-oxazoline)-co-(ethylenimine)] allows for a gene delivery system with a decreased toxicity. However, this comes at the cost of poor transfection efficiencies.1 Introducing complex polymeric architectures to these polymers affords an increase in transfection efficiency, whilst retaining the advantageous toxicity.2<br/>In this work, we provide a route towards the synthesis of poly[(2-methyl-2-oxazoline)-co-(ethylenimine)] with star-like architectures. An α-styrene functional poly(2-methyl-2-oxazoline) is first synthesised, followed by a RAFT-mediated copolymerisation with divinylbenzene to form the star polymer precursor. Acidic hydrolysis yields the poly[(2-methyl-2-oxazoline)-co-(ethylenimine)] copolymer, whose suitability as a gene transfection vector is evaluated.

Synthesis of 2-oxazoline ethylenimine copolymers possessing complex architectures

2019 Fall National Meeting

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