Towards more efficient gene therapy by investigating interactions of polyelectrolytes

Charged polymers, or polyelectrolytes (PE), are versatile synthetic materials which are used in purification of water, among other things.  The most important polyelectrolyte occurring among nature's macromolecules is DNA, which contains the human genome.

Many important applications of PE's are based on complexes formed of oppositely charged polymers, which however are sensitive to the presence of additional microions in the solution.

Hanne Antila, a doctoral candidate at Aalto University, began to model the interactions of polyelectrolytes in salt solution via computer simulations. It was revealed that the micro-ions in the solution unzip the links between polyelectrolytes (PE), that is, they replace the PE-PE links with ion-PE links one at a time. Unravelling of the links is affected by the ratio of charge densities of polyelectrolytes.

'I found two mechanisms through which the attractive interaction between a positively charged polymer and a negatively charged polymer can be turned into a mutually repellent form in a salt solution', Hanne Antila explains.

Guidelines for designing DNA carrier molecules

In gene therapy, the negatively charged DNA is complexed and in this way packaged into a positively charged carrier molecule. A good carrier molecule provides a sufficient protection for DNA in its way to the cell. To allow the genetic code contained by the DNA to be read, the carrier, however, must be able to free the DNA within the cell.

'In my work, I demonstrated how to influence the stability of the complex by controlling the charge of the carrier molecule and the salt concentration. The results, therefore, will be beneficial for the design of carrier molecules', Antila continues.

The results will also help in the development of multilayer coatings composed of alternative layers of oppositely charged polyelectrolytes. The unzipping phenomenon observed helps to explain the effect of the salt concentration on the speed of multilayer growth and on the multilayer stability.

The multilayer structures can be utilised, among other things, on metal surfacing to achieve desired features such as antimicrobial properties.

The study was made at the Department of Chemistry, in the Novel Materials Via Self Assembly research group led by Maria Sammalkorpi .

Dissertation

The public examination of the doctoral dissertation of M.Sc. (Tech.) Hanne Antila will be held on Thursday, 18 February 2016 at noon at Aalto University School of Chemical Technology in Lecture hall Ke2, Kemistintie 1, Espoo.

Doctoral dissertation Simulations of Polyelectrolyte Interactions in Salt can be read here (aaltodoc.aalto.fi).

More information:
Hanne Antila
Tel. 0500 563 674
[email protected]