New non-viral biocompatible nucleic acid delivery nanometric platform for controlled expression of foreign genes

We have developed a panel of synthetic nanohydrogels (NHGs) that complex nucleic acids with no cell toxicity. The final size of the complexes is pre-determined by the size of the nanohydrogel. Thus we can make 50, 200 and 400 nm sized NHGs/DNA complexes.

Interestingly, the complexes can be incubated with cells for undetermined period of time with no detectable cell toxicity.

We acknowledge that gene expression becomes significant 1 week after incubation. Expression of GFP and m-cherry plasmids last for at least 28 days in vitro and in vivo.

Unlike conventional lipo/polyplexes, our system can be incubated with cells for long periods without toxicity in vitro.

Our in vivo results suggest a continuous release of plasmids from the complexes with sustained protein expression along long period of time. Interestingly, the expression of the protein is found not only at the site of administration (SC and IM) but also at remote organs such as brain and heart as observed by post mortem histology in mouse.

The possibility of using our system for gene delivery of therapeutic, immunogenic or secreted proteins (gene therapy or vaccination) is now rationally supported by our in vivo results obtained after SC and IM administration of the complexes and their sustained expression for at least 28 days.