Method for Achieving High-Level Expression of Recombinant Human Interleukin-2 Upon Destabilization of the Rna Secondary Structure

摘要

The present invention provides a method for achieving high-level expression of the therapeutically important lymphokine (human IL-2). The method comprises of identifying the secondary structure in the 5' region of human IL-2 mRNA, modifying the 5' region of the human IL-2 DNA sequence to produce a new DNA sequence wherein the mRNA transcribed from the modified human IL-2 DNA sequence has the predicted 5' secondary structure destabilized with increased free energy compared to that of the secondary structure of the mRNA transcribed from the native DNA sequence without altering the sequence of the encoded amino acids; and using this modified DNA sequence of human IL-2 for high level recombinant expression in a microbial host for large scale production. This method is also applicable to other expression host like yeasts and mammalian cells.