BENGALURU: Researchers at the Indian Institute of Science (IISc) have created a better vehicle to carry genes into the body. The lipopolymer is made up of fat and repeating units of other chemicals.
The researchers attached a lipopolymer to an organometallic compound called ferrocene and another fat called DOPE (1,2-dioleoyl phosphatidyl ethanolamine).
It is more efficient and less toxic. Moreover, its unique structure allows control of timing and site of gene delivery, the researchers say.
Controlling ferrocene’s state allowed the researchers to gain control over the structure of the vehicle and, in turn, gene delivery.
When they oxidized ferrocene, the structure became loosely packed and gene uptake by cells dropped drastically.
When the researchers reduced ferrocene 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’ will allow researchers to pinpoint which population of cells should take up the desired gene and when, by tweaking ferrocene’s oxidation state as and when required, the researchers claimed.
Prof Santanu Bhattacharya, Chairman of Department of Organic Chemistry, and his team created the new vector.
“We could potentially deliver any therapeutic gene or molecules to the desired population of cells — for instatnce, Small interfering RNA (siRNA) to silence mutations or tumour protein p53 to stimulate cell death in cancer cells,” said Krishan Kumar and V Gururaja, PhD students and joint first authors of the upcoming Journal of Materials Chemistry B Paper.
Delivering specific genes inside cells to supplement missing and faulty genes or to silence disease-causing genes is a powerful tool towards gene therapy, they said.
Modified viruses are the most popular vehicles/vectors, but they are not only expensive but also highly toxic.
Recently, non-viral vectors have become popular, particularly lipopolymers which are more stable, less harmful and cheaper.
A nano-sized cocoon of lipopolymers surrounding a desired gene mimics the cell membrane’s make-up and can enter the nucleus where the gene needs to be delivered, they said.
Lipopolymers, called high molecular weight BPEIs and considered the ‘gold standard’ among non-viral vectors, are very efficient at gene delivery, but extensively toxic to cells.
By contrast, low molecular weight BPEIs are less toxic, but also insignificantly efficient.