Xiao, Su (NIDDK)
Martin, Scott (NCATS)
Betenbaugh, Michael (Johns Hopkins University)
Chen, Yui-Chi (NCATS)
This technology includes five microRNA mimics which were identified to improve the functional expression of hard-to-express membrane protein. These miRNAs are: hsa-miR-22-5p; hsa-miR-18a-5p, hsa-miR-22-3p, hsa-miR-429 and hsa-miR-2110. Improving expression level of recombinant mammalian proteins is vital, as the adequate supply of correctly folded proteins is the prerequisite for all structure and function studies. Rational attempts to improve membrane protein expression may not lead to expected results as membrane proteins involve particularly complex folding, assembly, and processing pathways, and there is only limited information for the bottlenecks that may reside in the protein production steps, such as transcription, translation, protein folding, secretion and cell viability. These miRNAs could be used to enhance expression of other membrane, intracellular or even secreted proteins with medical significance.
The discovered miRNAs could be used for engineering cell lines with enhanced productivity for membrane proteins for medical research as well as for therapeutic proteins and vaccines.
The capacity of miRNAs to globally regulate entire gene networks without introducing additional translational burden, compared with conventional overexpression strategies, makes them advantageous for the development of high producing cell lines.