Researchers at Indian Institute of Science (IISc) have developed a novel, controllable, extremely tiny vehicle to safely deliver genes into biological cells. The new vehicle, derived from a ‘lipopolymer’, is an improvement on known vehicles; it is more efficient and less toxic. Its unique structure also allows researchers to control the timing and site of gene delivery. Delivering specific genes inside cells to supplement missing and faulty genes or to silence disease-causing genes is a powerful tool in gene therapy.

Lipopolymers , as the name indicates, contain complex assemblies of fats and repeating chemical compounds. Prof Santanu Bhattacharya’s (chairman, Department of Organic Chemistry, IISc) group created the new vehicle by attaching ferrocene, a metallic compound that can switch between two chemical states, to a branched polyethylenimine (BPEI). This was then mixed with a ‘helper molecule’ – a naturally occurring lipid called 1,2-dioleoyl phosphatidyl ethanolamine (DOPE). Controlling ferrocene’s state allowed the researchers to control the vector’s structure, and in turn gene delivery. When they oxidised ferrocene, the vector’s structure became loosely packed and gene uptake by cells dropped dramatically. When they reduced ferrocenium by adding ascorbic acid (Vitamin C) to the cell culture, the vector became more compact and gene uptake by cells retained its original efficacy. This type of controlled ‘switch’ would allow researchers to pinpoint which population of cells should take up the desired gene, and when, by tweaking ferrocene’s oxidation state as needed.

“We could potentially deliver any therapeutic gene or molecule to the desired population of cells siRNA to silence mutations or p53 to stimulate cell death in cancer cells, for example,” explained Krishan Kumar and V Gururaja, IISc PhD students and joint first authors of the upcoming Journal of Materials Chemistry B paper.

Modified viruses are the most popular vectors, but they are not only expensive but also highly toxic to living cells. Recently, non-viral vectors have become popular, particularly lipopolymers. Lipopolymers are more stable, less harmful and cheaper to scale up than viral vectors. Such vectors may also be useful for gene transfer in agriculture or veterinary science, said Santanu Bhattacharya, senior author of the paper.

source: http://www.bangaloremirror.com / Bangalore Mirror / Home> Bangalore> Others / Bangalore Mirror Bureau / January 27th, 2015