Biopharmaceuticals are functional proteins or antibodies used in disease therapy that are produced by living cells in a bioreactor. Some of the more complex versions of these proteins must be made by mammalian (as opposed to bacterial or yeast) cells in order to be fully functional as medicines. In order to create the (recombinant) cell lines that produce the protein of interest, it is necessary to insert the DNA sequence coding for that protein into the genome of the cells. The methods currently used to accomplish this insertion event are somewhat antiquated and frequently result in detrimental cellular side effects such as unstable cell lines or poor product synthesis, as well as being time-consuming. Our research is focused on improving the manner by which the recombinant cells are created by developing strategies for inserting the exogenous coding sequence (for the product) in a highly specific, targeted way. Our approaches involve engineering the genome of a "master" cell line to contain targetable "recombination" sites into which any gene or sequence of interest may be inserted in a reproducible manner. These methods can also be applied to more basic research into gene function in cell-based models for diseases such as cancer and diabetes.
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Clarke C, Henry M, Doolan P, Kelly S, Aherne S, Sanchez N, Kelly P, Kinsella P, Breen L, Madden SF, Zhang L, Leonard M, Clynes M, Meleady P, Barron N. (2012) Integrated miRNA, mRNA and protein expression analysis reveals the role of post-transcriptional regulation in controlling CHO cell growth rate. BMC Genomics. 2012 Nov 21;13:656. doi: 10.1186/1471-2164-13-656.
- Piskareva, O. et al. (2007) Detection and cloning of LINE-1 elements in CHO cells. Cytotechnology. 2007 Apr;53(1-3):75-80.
- Barron N et al. (2007) Targeted Genetic Modification of Cell Lines for Recombinant Protein Production. Cytotechnology. 2007 Apr;53(1-3):65-73.