Updates and New Perspectives on Adenoviral Gene Therapy and Vaccine Vectors

Summary: In the 1990s, adenovirus was genetically engineered to selectively destroy cancer cells. Despite slow progress in translating oncolytic adenovirus to the clinic, interest in the virus remains strong. Many clinical trials are currently using recombinant adenovirus.

Summary: The adenovirus vector platform is an efficient toolbox for gene therapy, virotherapy, and vaccine development. The adenovirus genome and capsids can be modified using highly efficient techniques, and high-titer vectors can be produced to meet current needs. In recent years, the adenovirus vector platform has been extensively studied for the development of COVID-19 vaccines. The worldwide deployment of these vaccines has increased our knowledge on virus-host interactions and the need for further improvement.

Summary: An adenoviral-based vector system is a promising platform for vaccine development and gene therapy applications. However, high doses of the vector could lead to toxicity, and preexisting vector immunity in the body reduces the efficiency of the vector. Several strategies have been developed to overcome these challenges.

Summary: Carcinomas exhibit an upregulation of intercellular junctions that hinder immune response and drug therapy. The interaction between human adenovirus type 3 (Ad3) and Desmoglein 2 (DSG2) leads to a shedding of the binding domain and opening of tight junctions. The JO-4 protein, derived from Ad3, has been shown to enhance antibody therapy and chemotherapy effects. However, our study found that introducing the JO4 mutation to adenoviral vectors did not result in increased transduction in DSG2-high cell lines and weakened effects in DSG2-low cell lines. In fact, the JO4 vectors showed resistance in DSG2-negative cell lines possibly due to the negative effect of the JO4 mutation on the usage of another Ad3 receptor: CD46.