A natural polymer obtained from crustaceans is suitable for gene therapy

Gene therapy is a therapeutic strategy based on inserting genetic material into the cell in order to treat disorders caused by defective genes; that way, genetic defects can be corrected, the biological component needed for the therapy can be synthesised, or the effect caused by the gene responsible for the disease can be interrupted. So that the gene can reach the corresponding cell and the appropriate biological component be synthesised, it is essential to have a carrier that will protect the gene against enzymatic degradation, and which will facilitate its entry into the cell and that once it is inside can help it along its way to the nucleus. Therefore, it is essential that the carrier should take the gene all the way to the cell nucleus in a selective, effective way without causing any toxicity.

Researchers in the UPV/EHU's Department of Pharmacy and Food Sciences have proposed using chitosan polymers with a low molecular weight, oligochitosans, in gene therapy (chitosan is a natural polymer obtained from the outer skeleton of crustaceans). By means of a whole host of trials and rests, Mireia Agirre has shown in her PhD thesis that oligochitosans are capable of delivering large-sized nucleic acids (DNA) right to the cells and thus act on tumour cells and treat diseases of the central nervous system. As Agirre explained, "in this research we have shown that oligochitosans, unlike other polymers, are capable of delivering large plasmids (circular DNA molecules) although there are still things to be improved in terms of efficiency".

Oligochitosan and DNA nanoparticles

Oligochitosan and DNA form nanometric particles by means of electrostatic interaction (interaction between positive and negative charges). "We have been able to show that the transfection process is more effective in acid mediums. It should be pointed out that the tumour environment in our body is more acidic than normal, so it has been shown that these particles can be extremely useful in combating tumour cells," said the researcher. During this transfection process the particle is inserted into the cell and goes all the way to the nucleus and, once there, the protein that combats the disease is synthesised using the DNA contained in the particle.

In the research they did not use therapeutic DNA; however, "by means of tests using large, non-therapeutic DNA molecules," explained Agirre, "we have shown that if oligochitosans are used, the size of the DNA does not limit their possibility of going all the way to the nucleus and synthesising the corresponding protein". The researchers have also shown that these nanometric particles are capable of acting on human primary neuronal cells and, therefore, are of interest in treating diseases of the central nervous system.

As the researcher explained, "the next step in the research would be to test what has been discovered so far on animals, in specific applications and using therapeutic DNA. It would also be important to improve the particle so as to increase its efficiency".

Additional information

Mireia Agirre Diez, a graduate in Pharmacy, wrote up her PhD thesis entitled Polyplexes based on ultrapure oligochitosans: design, characterization and applications for gene therapy in the UPV/EHU's Department of Pharmacy and Food Sciences. Her PhD supervisors were Prof José Luis Pedraz and the lecturer Jon Zarate-Sesma.

Image: Image showing the nanoparticles entering human primary neuronal cells. The blue areas are the cell nuclei, the green ones are the cell cytoskeleton, and the red areas, the nanoparticles (Mireia Agirre / UPV/EHU).