Hokkaido University Research Profiles

Japanese

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  • Modification of Protein Translation Efficiency by Introducing Untranslated Region Sequences

    Three-digit increase or decrease in the expression efficiency of recombinant proteins by mimicking viruses

    By increasing the efficiency of protein expression per cell to 100 times the current level, we aim to dramatically increase the efficiency of recombinant protein production using CHO cells, etc., realizing a paradigm shift in genetic engineering technology.

    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.