Gene Therapy of Acquired Diseases and Cancer
The development of new vehicles (vectors) that allow for the efficient and stable transfer of genes in vivo opens up new opportunities for the treatment of different human diseases. HC-Ad are derived from adenovirus, but unlike previous versions, do not contain viral genes. This characteristic reduces their toxicity and endows them with two important properties: a large capacity to host genes and the ability to maintain their function for long periods of time. In light of their most frequent application, this would mean the endogenous production of therapeutic proteins for several years after a single administration of the vector.
Our group has perfected the method for producing HC-Ad to achieve greater yield and purity. The next challenge is to adapt this procedure to large-scale production under acceptable conditions for clinical use.
Antitumor therapy may prove to be an important application of HC-Ad. To date, most antitumor gene-therapy strategies have been shown to be very safe, but their efficacy is still low, partly because gene transfer inpatients is low and of short duration. HC-Ad may contribute to overcoming these limitations. In the laboratory, we have used HC-Ad capable of expressing immunostimulant genes such as interleukin 12 (IL-12) for long periods of time. Thanks to a system for controlling expression that can be induced using clinical drugs, we are able to maintain production of therapeutic levels of this protein, thereby favoring its antitumor activity and reducing side effects. In our animal models of bowel cancer, this treatment is able to eradicate the tumors in most mice, especially when used in combination with chemotherapy. We are currently developing new HC-Ad equipped with a combination of genes to achieve greater stimulation of the immune response to tumors, and we hope to prepare new treatment protocols for bowel, liver and pancreatic cancer.
With future applications in mind, we are exploring the possibility of using the properties of HC-Ad to transfer all the genetic material needed for the therapeutic modification of the genome in vivo. The aim is to achieve the correction of genetic mutation or the integration of genes in specific locations on the genome of an organism. Although there are still many obstacles to overcome, this would mean, for the first time, a definitive etiological treatment for genetic diseases.