Gene Therapy entails the delivery of new genetic information to cells so that their function is altered.
The tremendous advances in molecular medicine and biology within the last decades have led to the development of promising therapeutic tools for the treatment of cancer, genetic defects, infectious diseases or tissue injury. These include the generation of gene-based approaches such as the correction of defective genes or the over-expression of therapeutic molecules
The tremendous advances in molecular medicine and biology within the last decades have led to the development of promising therapeutic tools for the treatment of cancer, genetic defects, infectious diseases or tissue injury. These include the generation of gene-based approaches such as the correction of defective genes or the over-expression of therapeutic molecules.
By delivering specific genetic information, researchers have the ability to deliver a therapeutic effect by correcting an existing abnormality or providing cells with a new function, by influencing how the cell behaves, its function and how it responds to injury. The central hypothesis of the REMEDI programme focuses on the genetic modification of cells or tissues such as Mesenchymal Stem Cells (MSCs) or Endothelial Progenitor Cells (EPC) transplantation for many different treatments. These treatments and therapies to promote tissue regeneration and/or repair for severe diseases including myocardial infarction (MI), osteoarthritis (OA), spinal cord injury or peripheral vascular disease (PVD).
One of the main difficulties with gene therapy is how to deliver this genetic material to cells. This is achieved by using vectors which carry the material into the cell. The most common vector is an engineered virus which has been rendered incapable of replication and is now carrying the gene product.
A major focus of the gene therapy research in REMEDI is to develop safe and efficient vectors for the transfer of genetic material to cells like Mesenchymal Stem cells. In the majority of clinical trials adenoviral and retroviral vectors have been used to deliver the genetic material. A variety of different viruses and non-viral means are being explored at REMEDI with a focus on Adenoviral and non-viral vectors. In addition REMEDI also investigates the development of novel site-specific integration systems for long-term gene expression.
Most Adenoviral Vectors are based on serotype 5 of the human adenovirus and have been used in several clinical trials for therapeutic gene transfer in humans. The Viral vector is deleted in E1 and E3 genes rendering it replication incompetent, this allows it to act as an extremely efficient and safe vector for gene transfer to both dividing and non-dividing cells. However, adenovirus vectors induce a cascade of immune reactions against the vector itself and against the transduced cells or tissues which finally leads to short-term (transient) expression of the desired transgene. Therefore more research is required to understand the immune and cellular responses to these vectors and this is one of the major aims of REMEDI. Moreover the development of low-immunogenic adenoviral vectors which reduced immunogenicity is a major focus of REMEDI. These vectors will then be used to transduce mesenchymal stem cells in vitro or for direct injection e.g. into the vasculature.
As described earlier, viral vectors may lead to undesirable side effects. Undoubtedly synthetic vectors may have advantages over viral vectors in terms of toxicity and potential induction of immune responses. They are also industrially reproducible allowing easier pharmaceutical development, quality control and scalable production. In REMEDI, a specific synthetic vector system for MSC transfection will be designed by focusing on the 3 elements which make the viral vector so efficient; the structure of the lipoplexes (DNA/lipids complexes); REMEDI’s proprietary antibodies for specific targeting of MSC; and elaborating host genome site specific integration for stable gene expression, if needed.