Projects / Programmes
Treatment of malignant tumours with electrogene therapy
| Code |
Science |
Field |
Subfield |
| 3.04.00 |
Medical sciences |
Oncology |
|
| Code |
Science |
Field |
| B200 |
Biomedical sciences |
Cytology, oncology, cancerology |
malignant tumours, electroporation, electrogene therapy, plasmid DNA, p53, IL-12, mouse tumour models, dogs
Researchers (9)
Organisations (1)
| no. |
Code |
Research organisation |
City |
Registration number |
No. of publicationsNo. of publications |
| 1. |
0302 |
Institute of Oncology Ljubljana |
Ljubljana |
5055733000 |
15,471 |
Abstract
Armed with the knowledge of the molecular anatomy of the cancer cell, gene therapy has emerged as a new method of therapeutic approach in cancer treatment. In the development of gene therapy one of the major focuses of research is the efficient and safe transduction of target cells. An ideal gene transfer method would allow introduction of sufficient concentration of DNA into the desired target cells with minimal side effects. Standard transfer methods employ retroviruses and adenoviruses. Other approaches for gene delivery include liposomes, cationic lipids, direct injection, bombarding cells with particles coated with DNA and electroporation (electrogene therapy), which already proved high efficiency as a safe non-viral gene delivery method.
In the proposed project we will deal with three aspects of electrogene therapy. In the first part, we will address further optimisation of electrically-assisted gene delivery. We plan to use biochemical modification of extracellular matrix of tumours using hyaluronidase and collagenase in combination with most suitable electrical condition to potentially further increase transfection efficiency. We are planning to use two enzymes: hyaluronidase and collagenase, which specifically target component of extracellular matrix and should consequently increase diffusion coefficient of macromolecule DNA, which should lead to better distribution of DNA throughout the tumour mass.
In second part of the proposed project development of successful electrogene therapy using RNA interference (RNAi) targeting tumour suppressor gene p53 is foreseen. Due to its great specificity to target RNA molecules, RNAi has also big potential in treatment of cancer. Our goal is to use siRNA-targeting p53, which will enable us to further investigate the role of p53 in treatment of cancer.
Third part of the project is aimed to broadened electrogene therapy from local to systemic tumour treatment by using electrically-assisted IL-12 delivery to muscle. The choice of plasmid DNA coding for IL-12 for this part of the project is based on the known facts that IL-12 has dual effect on tumours; one is through activation of cytotoxic T lymphocytes (CTL) and the other through antiangiogenic action.
To facilitate translation of this therapy into clinical practice, immunogene therapy will be tested in treatment of primary tumours of different histological origin in dogs after debulking of tumour mass by surgery or after systemic chemotherapy.
All together, the proposed project is composed in a such a way that it will cover elucidation of basic mechanisms, which are involved in gene delivery, and the role of p53 in cancer treatment, as well as translational research bringing electrogene therapy using silencing of p53 and immunogene therapy using Il-12 into both, veterinary and human medicine.
