Projects / Programmes
Razvoj novih oblik nanodelcev TNF-alfa za uporabo v terapiji (Slovene)
| Code |
Science |
Field |
Subfield |
| 4.06.01 |
Biotechnical sciences |
Biotechnology |
Recombinant DNA technology |
| Code |
Science |
Field |
| 3.04 |
Medical and Health Sciences |
Medical biotechnology |
Researchers (18)
Organisations (2)
Significance for science
Controlled preparation of protein nanoparticles for pharmaceutical and medical purposes is a challenge for science as well as for technology and still waiting for right solutions. Although virus particles, more precisely, the structure of the virus protein coat, presents a good example from nature, a great majority of rules developed by nature for virus particle assembly still cannot be directly applied in practice. The main contribution of our project is an original way of preparation of protein nanoparticles, which is based upon numerous relatively weak interactions among metal ions and electron donor groups on the protein molecules. An interesting property of such interactions is that they can be easily interrupted by changing environmental conditions, which can be applied as an advantage to design "smart" responding nanoparticles.
In this project we were able to show that with the use of zinc ions, small polifunctional chelating agents or dendrimers with chelating function and histidine rich proteins, nanoparticles of various sizes can be formed and that the basis for the binding is coordinative bond. We were also able to prepare inorganic (phosphate) nanoparticles with zinc ions on the surface, which are also suitable for binding proteins through coordinative bond. In addition to in vitro preparation of number of nanoparticles based on TNF, we also managed to produce particles in vivo, with expression in yeast Pichia pastoris. These particles would be particularly useful for use in anti-TNF therapy, due to reduced biological activity and could be sufficiently immunogenic to trigger active immunization.
Significance for the country
Or project “Novel approaches to formation of TNF-alpha nanoparticles: Implications for advanced therapies” found solutions to design “smart” protein nanoparticles, capable of sustained release of active ingredient at the target, for instance tumor tissue. Using such particles the surrounding tissues would be less affected by toxic side effects of the therapeutic molecule as compared to usual therapies using active molecules themselves. These studies are leading to efficient next generation protein biopharmaceuticals, with preserved efficacy of usual protein biopharmaceuticals but with beneficial properties for the patient. Worldwide, in the field of pharmaceutics, research on the next generation protein biopharmaceuticals is classified as the most advanced appoach. The investigated principles of nanoparticle formation are widely applicable to numerous proteins, therefore our industrial partner Pharmaceutical Company Lek d.d. strongly supports the research, which leads to very good collaboration between academia and Slovenian pharmaceutical industry. Today Lek, partly due to similar forms of collaboration in the past, takes part in the modern development trends and builds new capacities for production of recombinant biopharmaceuticals. This kind of collaboration also offers the reverse information from industry to academia, how to lead the research work to obtain valuable information that could serve as a basis for development of actually useful industrial procedures and products.
On the other hand, our project employs numerous young people, at the graduate or post-graduate level, thus contributing to formation of young generation researchers that the high-tech pharmaceutical industry will need in the future. Three researchers from the project group during the project moved into the development departments of Lek d.d. and occupied significant positions there. Educated and motivated workers are the main assurance for development and operation of high-tech enterprises.
Most important scientific results
Annual report
2009,
2010,
2011,
final report,
complete report on dLib.si
Most important socioeconomically and culturally relevant results
Annual report
2009,
2010,
2011,
final report,
complete report on dLib.si
