Plasmid DNA for Gene Therapy and DNA Vaccine Applications, 2nd Edition

Dear Colleagues,

In recent years, there has been an increased interest in plasmid DNA as a vector for gene therapies and DNA vaccines against infectious, acquired, and genetic diseases, including cancer and COVID-19. Additionally, plasmids are used for the production of viral particles intended for viral gene and oncolytic therapy. With the recent event of artificial gene synthesis methods, the assembly of new plasmids has become easier than ever. Plasmids can be designed to encode for various therapeutic targets, vaccine antigens, therapeutic antibodies, shRNA molecules, elements of CRSPR/Cas9 systems, viral vector elements, etc. Additionally, expression cassettes can now be easily tweaked and codon-optimized for higher and more targeted expression, and bacterial backbones minimized for more efficient and safer plasmid production. However, there are still some challenges that need to be overcome to achieve the widespread application of plasmid DNA therapeutics. First of all, as plasmids do not enter cells actively, their therapeutic success depends heavily on physical and chemical delivery methods, which are constantly being developed and optimized. Secondly, the exact mechanisms leading from a plasmid’s cell entrance to its expression in the nucleus remain elusive. Thirdly, although considered less immunogenic than viral vectors, plasmid DNA still activates a cell’s defense mechanisms against foreign DNA. While this self-adjuvanting effect of plasmid DNA can be advantageous for applications in DNA vaccination and cancer gene therapy, it can uncontrollably influence transfection efficiency and safety. Finally, there are still some challenges in preparing large quantities of clinical-grade plasmid DNA.

This Special Issue welcomes research papers dealing with all aspects of gene therapy and DNA vaccine applications of plasmid DNA: from basic plasmid design studies, mechanistic studies of plasmid fate inside cells, and the testing of new therapeutic approaches or new plasmid delivery systems to large-scale manufacturing and regulatory compliances of plasmid DNA therapeutics as well as their clinical applications. Review articles on the abovementioned topics are also welcomed.

Dr. Urska Kamensek
Guest Editor

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