Non-viral Vectors for Gene Therapy

Presently, more than 3400 genes have been associated with diseases [1], some of these pathologies are debilitating, mortal, and without any effective therapeutic options, and this number is expected to increase in the next decade as genomic studies advance. Gene therapy is a therapeutic strategy that seeks to target the genes behind the disorders in order to cure patients. Thus, this approach holds the promise of establishing therapies that treat the causes, rather than the symptoms, by manipulating deficient genes, removing or silencing pathologic genes, or adding missing genes. However, these ambitious strategies have been hampered by several problems, such as the lack of safety and efficiency of some of the developed approaches, which can be explained by the very nature of most gene-manipulating tools. Naked DNA plasmids, for example, are rapidly degraded in biological fluids, they are unable to efficiently cross the cellular membranes and therefore reach the target cells and they activate the immune system, which is programmed to identify and eliminate vehicles containing foreign genetic information [2]. Thus, although a large number of preclinical and clinical studies have been performed using naked nucleic acids, the use of delivery vectors yields better results, namely because they protect the nucleic acids from nuclease degradation and increase intracellular delivery. Still, despite the big efforts made in the last decades with gene therapy strategies, very few gene therapy-based drugs or therapeutic products have reached the market, revealing that much still has to be done in the field of vectors for gene therapy.