DNA-vaccines use DNA fragments instead of whole pathogens to elicit a specific immune response and are safe, easy to mass produce, and can be administered with a sticker patch.
DNA-vaccines provide a new approach to immunization and immunotherapy in which genes that encode for antigen proteins are inserted into the nuclei of appropriate cells of the affected host in order to use those cell’s own protein-making machinery to express proteins designed to elicit a strong immune response against the disease-causing pathogen. This ability to stimulate the immune system to defend against serious infections via DNA-induced immunization is far-reaching and profound, since it may be possible to develop vaccines against any pathogen whose genome is known. It has been stated that in a serious worldwide epidemic, if gene-vaccines are sufficiently developed, a single laboratory would be able to produce enough DNA in one week to immunize not only a city but the entire world. However, there are many significant challenges that need to be overcome for the promise of gene vaccines to be fully realized, and one of the most important is solving the delivery problem.
DNA-vaccines
In a serious worldwide epidemic, if DNA-vaccines are sufficiently developed, a single laboratory would be able to produce enough DNA-vaccines in one week to immunize not only a city but the entire world
DNA-vaccines are expected to have between 5,000 and 20,000 nucleotide base pairs because aside from carrying the antigen genes, they also carry promoter genes and other genes that encode for cytokines and other supportive proteins. The delivery these long plasmids into the nucleus of appropriate cells, which ideally would be antigen-presenting cells such as dendritic monocytes, remain an enormous challenge to date. Although attenuated viruses are capable of transfecting cells with many genes and have been investigated as potential delivery systems, there are significant concerns regarding their safety. For example, the attenuated form of the poliovirus is known to reverse to its virulent state in-vivo causing wild-type polio. Additionally, the most widely used viral vector, the adenovirus, has the drawback of being antigenic in itself, which means that a pre-existing immunity to it may limit their potency due to the fact that the body would clear the viral vector before it can infect cells to deliver its payload of antigen genes.
On the other hand, synthetic materials with DNA delivery properties are a viable alternative with ample potential for innovation. Our research focuses on the direct delivery of DNA-vaccines to professional antigen-presenting cells such as the Langerhans dendric cells that are present in the epidermis of the skin using novel stimuli-responsive microneedle patches.
Selected Publications
Cruz, I.; Gomez, C.; Alarcon, H. Montano, G.; Pardo, A.; Armijos, R.; Noveron, J.C. Alkyl Length Effects on the DNA Transport Properties of Cu (II) and Zn(II) Metallovesicles: An In Vitro and In Vivo Study. Journal of Drug Delivery, 2018, vol. 2018, 2851579
Tasnim, N., Nair, B.G., Sai Krishna, K., Kalagara, S., Narayan, M., Noveron, J.C., Joddar, B. Frontiers in Nano-therapeutics. Springer, 2017.
Pal, S.; Islam, T.; Moore, J.T., Reyes, J.; Pardo, A.; Varela-Ramirez, A.; Noveron, J.C. Self-assembly of a novel Cu(II) coordination complex forms metallo-vesicles that are able to transfect mammalian cells. New Journal of Chemistry, 2017, 41, 11230 - 11237.
What are the expected innovations in this area?
DNA-vaccines will lead efforts in preventive medicine against existing and emerging infectious diseases
DNA-vaccines can be developed for any pathogen whose genome is known. A critical challenge is to develop (1) stimuli-triggered delivery systems, (2) fast-acting, stable mRNA-vaccines that circumvent the cell's nucleus, (3) suitable adjuvants for DNA/RNA-vaccines.