CHO cell lines have been used in upstream biomanufacturing for at least the past four decades, particularly for blockbusters like Rituxan, Humira and Enbrel. Last year, scientists were able to sequence the Chinese hamster genome to aid bioprocessing systems analysis and cell line engineering.
But the misidentification of cell lines has been a problem in the scientific community “for the past 50 years,” according to NIST. In an attempt to battle this, NIST researchers have developed multiplex assays that offer unique short tandem repeat (STR) marker profiles for mouse samples. The assays can be used to authenticate mouse cell lines, which could aid in the quality control and detection of contamination, according to a study published in Cytotechnology in January.
NIST scientists to date have identified nine STR markers specific to CHO DNA and seven markers have been used in a multiplex assay.
Since the publication of its efforts, the NIST team has partnered with DNA testing lab DDC Medical to commercialize mouse cell line authentication using STR DNA technology. The DDC Medical mouse cell line authentication test uses STR DNA analysis to characterize the mouse DNA. The loci selected produce stable, robust results based on a tetranucleotide repeat, similar to the types of loci examined for human cell line authentication.
“We are also working on STR assays for rat cell lines,” Dr. Kenneth Cole, Deputy Group Leader of NIST’s Biochemical Science Division, told us. As far as how long that work may take, he said it’s hard to predict though “it will be a while, we have to finish the assay and test a number of cell lines and rat strains, that takes a while.”
Other NIST Biomanufacturing Projects
NIST’s work in biomanufacturing is wide ranging, with other projects focusing on protein structure and stability, as well as biomanufacturing-related standard reference materials and CHO cell production metrology.
Anne Plant, chief of the Biosystems and Biomaterials Division at NIST, explained to us that NIST doesn't unilaterally set standards, but that the institute convenes communities that then set standards by consensus.
“NIST has a big footprint in protein therapeutics,” Plant told us. “Cell therapies are coming up strong as another component that has unique challenges.”
For research and development labs to understand what other labs have done if there isn’t a basis of comparison of measurements is difficult so “they look to us to help them figure out what measurements are important and how to make them traceable,” she said, predicting this will “go on for some time” as cell therapies are a new type of product and biomanufacturing process.