Content of research

Human adenoviruses, which have long been used for gene transfer, are a typical example of a viral vector system with a proven safety profile. Although wild-type adenoviruses have a remarkable ability to shut down host protein expression during infection and express their own late-phase proteins preferentially and explosively, they have not received much attention. Since adenoviruses themselves are pathogenic; however, the use of their viral particles in recombinant protein purification systems is problematic in terms of safety. Therefore, we aim to optimize the leader sequence in the viral gene and incorporate it as an untranslated region sequence upstream of the recombinant protein, so that we can mimic the viral translation system and increase the translation efficiency from existing expression vectors by more than 100-fold. Conversely, it is also possible to modify the untranslated region downstream of the termination codon to reduce the expression level by a factor of several dozens.

Potential for social implementation

• ・Massive expression of recombinant proteins that is difficult with E. coli and insect cells
• ・By optimizing the expression level of recombinant proteins, stable and efficient iPS cell establishment can be achieved.
• ・Application to mRNA injection experiments (introduction of specific sequences into the untranslated regions of mRNA)

Appealing points to industry and local governments

This research is unique since it is aimed to achieve a three-digit increase (or decrease) in the efficiency of protein expression by introducing a specific sequence into the untranslated region of transcribed mRNA, rather than improving the promoter. It is also possible to easily generate mammalian recombinant cells, which have been difficult to establish in the past, by strengthening or weakening intracellular expression.