Approaches in Gene Therapy of Cancer and Cardiovascular Diseases

Abstract

In this chapter we will focus on few topics. First, we summarize and discuss angiogenic gene therapy of cancer and cardiovascular diseases, with RNA interference in a separate section. Second, we briefly review delivering systems in gene therapy, their advatages and limitations and further focus on bacterial vectors. Last, we summarize antioxidant gene therapy of cardiovascular diseases and hypertension. Considering the fact that the fundamental discoveries and new findings in medicine are being crystallized on genetic and genomic levels, gene therapy is one of the potential mechanisms for therapeutic intervention. Gene therapy in a broad sense, i.e. all the therapeutic strategies employing nucleic acids as carriers of genetic information, found its utilization in most areas of medicine, including angiogenesis research. Similarly to classical “non-gene“ therapy, the research in gene therapy is happening on the preclinical level using appropriate animal models, with cancer and cardiovascular diseases being the most abundant indications. There are several different strategies known. Besides the delivery of therapeutic gene (replacement of the mutated gene by a functional one or delivery of the gene because of lack of the gene product), novel strategies are also being widely used based on blocking the function of a specific gene by application of RNA interference inducing sequences, antisense inhibition etc. One of the key advantages of gene approaches is the endogenous production of the therapeutic molecule. Furthermore, targeted gene delivery specifically into the target tissue or only to a certain cell type can dramatically decrease the likelihood of adverse effects. Along with the development of new vectors and regulatory systems, the ability to control the expression of therapeutic gene in time and space is being improved. This is of great importance in affecting such complex and complicated processes as angiogenesis. Currently, almost three quarters of indications addressed by gene therapy clinical trials are represented by cancer and cardiovascular diseases