Basic and translational research
Many different groups at the Institute are conducting the basic and translational research on gene therapy for Cancer Research at the Norwegian Radium Hospital. Some research is being executed at the core facility as described above, but a considerable amount of research, not requiring special facilities, also take place in the ordinary research laboratories at the Institute.
The research is focused on the use of small molecular substances in gene therapy, immunogene therapy, targeting adenoviral gene delivery and the use of drug resistance genes in the gene therapy of normal and malignant cells. In addition, research groups have initiated searches for new gene therapy targets.
The groups focused on the use of small molecular substances are using ribozymes or antisense molecules, oligonucleotides targeted to a variety of genes of importance to the phenotype and malignant behaviour of tumour cells. The molecules used for this purpose are in the form of synthetic ribozymes; oligonucleotides or ribozymes delivered by the use of adenoviral expression vectors. Another way of ribozym delivery is mediated by liposoms, which can be administered locally into tumours. Ribozymes can be targeted to inhibit various signaltransduction pathways, which protects the cells from apoptosis, targeted against cytokines and growth factors such as VEGf and bFGF and TNF a. The research governing the field of immunogene therapy, has been focusing on improved transfection efficiency using electroporation to transduce isolated dendritic cells with mRNA for antigen expression. Two different approaches have been used in the research on targeted delivery of therapeutic genes. Such genes may be delivered by specific transcription in cells of interest, using tissue or cell specific promoters. Such promoters are then used in conjunction with the delivery of a therapeutic gene. With the other approach, the selectivity of gene delivery to the region of interest is achieved by the use of light. In this principle, known as photochemical internalisation, the light may activate the photosensitiser located in the membranes of lysosomes, which then results in the liberation of phagocytosed molecules and gene therapeutic vehicles into the interior of the cells.
As the bone marrow toxicity is one of the major limitations of cytotoxic therapies, the transfer of drug resistance genes into bone marrow stem cells, may enable the stem cells to withstand damage from cytotoxic drugs allowing much higher drug doses than commonly to be used. The stem cells are transduced by the use of retroviral vectors. In addition, both a new subtraction cloning technique and array systems are employed in the search for new gene therapy targets in malignant cells.
The research is focused on the use of small molecular substances in gene therapy, immunogene therapy, targeting adenoviral gene delivery and the use of drug resistance genes in the gene therapy of normal and malignant cells. In addition, research groups have initiated searches for new gene therapy targets.
The groups focused on the use of small molecular substances are using ribozymes or antisense molecules, oligonucleotides targeted to a variety of genes of importance to the phenotype and malignant behaviour of tumour cells. The molecules used for this purpose are in the form of synthetic ribozymes; oligonucleotides or ribozymes delivered by the use of adenoviral expression vectors. Another way of ribozym delivery is mediated by liposoms, which can be administered locally into tumours. Ribozymes can be targeted to inhibit various signaltransduction pathways, which protects the cells from apoptosis, targeted against cytokines and growth factors such as VEGf and bFGF and TNF a. The research governing the field of immunogene therapy, has been focusing on improved transfection efficiency using electroporation to transduce isolated dendritic cells with mRNA for antigen expression. Two different approaches have been used in the research on targeted delivery of therapeutic genes. Such genes may be delivered by specific transcription in cells of interest, using tissue or cell specific promoters. Such promoters are then used in conjunction with the delivery of a therapeutic gene. With the other approach, the selectivity of gene delivery to the region of interest is achieved by the use of light. In this principle, known as photochemical internalisation, the light may activate the photosensitiser located in the membranes of lysosomes, which then results in the liberation of phagocytosed molecules and gene therapeutic vehicles into the interior of the cells.
As the bone marrow toxicity is one of the major limitations of cytotoxic therapies, the transfer of drug resistance genes into bone marrow stem cells, may enable the stem cells to withstand damage from cytotoxic drugs allowing much higher drug doses than commonly to be used. The stem cells are transduced by the use of retroviral vectors. In addition, both a new subtraction cloning technique and array systems are employed in the search for new gene therapy targets in malignant cells.