Projects / Programmes
Development of production and purification processes for adenoviruses
| Code |
Science |
Field |
Subfield |
| 4.06.00 |
Biotechnical sciences |
Biotechnology |
|
| Code |
Science |
Field |
| P003 |
Natural sciences and mathematics |
Chemistry |
| P300 |
Natural sciences and mathematics |
Analytical chemistry |
| B002 |
Biomedical sciences |
Biophysics |
adenoviruses, virus vectors, chromatography, CIM monolithic chromatographic supports, gene therapy
Researchers (1)
| no. |
Code |
Name and surname |
Research area |
Role |
Period |
No. of publicationsNo. of publications |
| 1. |
22444 |
PhD Barbara Lah Jarc |
Biotechnology |
Head |
2007 - 2008 |
0 |
Organisations (1)
Abstract
Adenoviral vectors are very popular in gene therapy, because of the easy entrance into the cells. Traditional methods of adenovirus purification are long-standing and inefficient in the scale-up , industry processing. It is our aim in this project, to establish and optimise processes for adenoviral production in cell lines, to develope methods for detection and quanitification of viral particles and subsequently establish and optimise processes of adenovirus purification on CIM monolithic chromatographic supports. CIM monolithich supports represent a new generation of chromatographic supports for purification and separation of proteins, polynucleotides and viral particles. Based on convective interaction media transfer, monoliths offer flow rate independent properties like capacity, separation and yield. High dynamic capacities of large molecules and virus particles and high flow rates at low pressure drops are characteristic for monolithic supports. All these characteristics of monoliths offer up to one grade better and more efficient down-stream processing in virus production and purification in comparison to classical chromatographic methods. The expected result of the project will be validated method for adenovirus production and purification on CIM monolithic chromatographic supports.
Significance for science
Adenoviral vectors are very popular in cancer gene therapy because they easily enter human cells. For such applications high titre and high purity biological material is required. Even though there are many different methods of biological material purification available, chromatography still represents the method of choice, when the requests for high purity of biological material must be met. Nowadays, stationary phases that are mechanically and chemically stable and have high capacities for target molecules are desirable. High capacity and selectivity of stationary phases for target molecules are very important for purity of selective compound. As monolithic supports offer faster separations, consequently faster processes and higher productivity can be achieved in the field of biopharmaceutics. CIM monolithic chromatographic supports represent a new generation of chromatographic supports where fast mass transfer is based on convective flow. While dealing with particles based chromatography, capacities and separations depend on flow rate since molecules needs to diffuse into the pores. Based on convective interaction media transfer, monoliths offer flow rate independent properties like capacity, separation and yield. All these characteristics offer a great potential in preparative chromatography for large biomolecules such as viruses (i.e. adenoviruses, influenza viruses), proteins and DNA. Consequently, monoliths are becoming a real alternative to classical porous particle based chromatography.
Established and optimized processes for adenoviral purification, based on CIM monolithic ion exchange chromatographic supports, are very important links for technical transfer from laboratory to industrial scale. High dynamic capacities for large molecules (i.e. viruses), high flow rates at low pressure drops and high biologic activity of purified molecules are characteristic and unique for CIM monolithic supports. The purification processes are fast and large quantities of purified biological material can be prepared for further clinical trials. We believe, established chromatographic processes of adenovirus purification could be further transferred to Parvovirus i.e. "adeno associated viruses", important gene therapy virus candidates.
Significance for the country
Due to current increases in development of new large molecule based pharmaceuticals and due to the lack of suitable purification technologies, the development and production of monolithic supports, along with purification methods (i.e., purification of viruses, proteins, DNA), presents a strategically important technology to BIA Separations. We are creating knowledge that can be used for breakthrough to new biotechnology markets (i.e. contract research). This technology will give Slovene pharmaceutical companies a competitive edge, since it assures increased productivity in macromolecules production and thus lowers costs in preparation of biogenerics.
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