Projects / Programmes
Development and implementation of novel approaches to solve purity and quality challenges of therapeutic viruses
| Code |
Science |
Field |
Subfield |
| 4.06.00 |
Biotechnical sciences |
Biotechnology |
|
| Code |
Science |
Field |
| 3.04 |
Medical and Health Sciences |
Medical biotechnology |
therapeutic viruses, adeno-associated virus, downstream purification, analytical methods, digital PCR, high-throughput sequencing, electron microscopy, genome integrity
Data for the last 5 years (citations for the last 10 years) on
June 28, 2024;
A3 for period
2018-2022
Data for ARIS tenders (
04.04.2019 – Programme tender,
archive
)
| Database |
Linked records |
Citations |
Pure citations |
Average pure citations |
| WoS |
337 |
10,098 |
9,079 |
26.94 |
| Scopus |
337 |
11,587 |
10,483 |
31.11 |
Researchers (13)
Organisations (3)
Abstract
Precision medicine is becoming more and more important and viral vector based therapies are one of the first steps towards improved medical treatment. Development of new, improved therapeutics for genetic diseases and disorders are needed. Viral characteristics enable them to act as delivery agents or vectors and are used as vaccine platforms, as anti-cancer agents, and as vectors in gene therapy. Adeno-associated viruses (AAV) are one of the most widely used vectors for viral based gene therapy and are applied in numerous gene therapy programs. AAVs can naturally infect dividing and non-dividing human cells, have never been linked to any disease and they cause no or mild immunogenic response. Within the proposed project we will focus on the Adeno-associated viruses (AAV) that are most widely used vectors in gene therapies. Their application is regulated regardless of their origin and they encounter several restrictions prior to application to patients. Purity, quantity and quality are the most important attributes of the therapeutics that needs to be assessed. The proposed project aims to development and implementation of novel analytical and processing approaches to improve the current state-of-the art technologies for production, downstream purification and analytical characterization of the therapeutics. Current products still contain too many impurities in the form of unwanted nucleic acids within the viral capsids. Therefore, the main objective of the project will be to understand the content of viral vectors, especially the integrity of the genome and the presence of impurities, which we will achieve by developing new analytical approaches. At the same time, we will develop a new vector purification process and compare it with the currently used options for further processing, where we will accurately characterize the different steps or fractions, by using different newly developed approaches including high-throughput sequencing. With the information obtained on the content of viral vectors, we will then begin to develop strategies to reduce the possibility of incorrect packaging of the unwanted DNA into capsids. In particular, we will focus on the obtained sequence data and evaluate the formation of chimeric sequences with in silico analysis, which are one of the reasons for incorrect packaging. The ultimate goal is the transfer of developed technologies to industry. To achieve the goals we have assembled an interdisciplinary team of excellent scientists in combination with companies. Project partners, National Institute of Biology, EDUCELL and ICHORLABS, will be supported also by International Centre for Genetic Engineering and Biotechnology from Trieste, which has AAV production facility and lots of experience with AAV production. We also have an agreement with J. Michael Hatfield, who recently retired from AveXis (Novartis Gene Therapies), to have a role as scientific advisor to the project. Most direct impact of the project would be in the form of technology transfer of the selected analytical methods and newly developed approaches to EDUCELL and other potentially interested companies, which will get access to cutting edge technology, at the same time they would get a possibility of time-and cost-effective analytics. We expect that the project results will enable comprehensive understanding of the actual content of viral particles, by solving the challenges of purity and quality of therapeutic viruses and offering solutions for their improvement in the future. This will ensure availability of a drug product that is safe, efficacious and of high quality, which will be of benefit to the receiving patients.
