Genetic Engineering & Biotechnology News

NOV15 2017

Genetic Engineering & Biotechnology News (GEN) is the world's most widely read biotech publication. It provides the R&D community with critical information on the tools, technologies, and trends that drive the biotech industry.

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24 | NOVEMBER 15, 2017 | | Genetic Engineering & Biotechnology News track any significant changes in genotype throughout an experiment (Figure 4). Case of Mistaken Identity or Mismatch Repair In addition to genetic drift and chromo- somal rearrangements, many widely used cell lines, such as HEK293, CCRF-CEM, and Jurkat, have acquired mutations in mismatch repair genes. Commonly cited as a causative factor in cancer formation, these mutations compromise a cell's ability to repair mistakes made during DNA replication. According to Markus Schmitt, Ph.D., founder and CEO of Multiplexion, cell lines with this genetic in- stability "have been shown to acquire chang- es in their STR profile upon long-term culture that can lead to false authentication results." Although profiling additional STR mark- ers can improve authentication results for cell lines with deficiencies in their mismatch re- pair system, Multiplexion has developed an alternative approach for cell lines likely to be misclassified by STR profiling. Instead of us- ing STR loci, the company's Multiplex Cell Authentication (MCA) service uses a multi- plex assay to simultaneously test 24 single nucleotide polymorphism (SNP) loci in the genome to authenticate human cell lines. "Multiplexion's cell line authentication sys- tem is a cost-effective alternative to STR profil- ing," commented Dr. Schmitt. Currently, Mul- tiplexion's "steadily growing" database includes 850 of the most frequently used human cell lines. Data from cell-based experiments forms the foundation for preclinical studies that lead to advances in disease prevention and treatment. After 50 years, cell line contamination and mis- identification continue to undermine that foun- dation. Despite efforts to raise awareness and to make methods for cell line authentication accessible, the majority of scientists working with cell lines continue to forgo this important quality control test. Discussions around the barriers preventing scientists from adopting cell line authentication protocols are in prog- ress, but it may take external pressure from grant-funding agencies and scientific journals to reinforce the integrity of scientific studies. References 1. J.J. Boonstra et al., "Verification and Unmasking of Widely Used Human Esophageal Adenocarcinoma Cell Lines," J. Natl. Cancer Inst. 102(4), (2010). 2. R. Harris, "Mistaken Identities Plague Lab Work with Human Cells (radio broadcast episode), (December 9, 2014), shots/2014/12/09/368491013/mistaken-identities- plague-lab-work-with-human-cells, accessed October 20, 2017. 3. L.P. Freedman et al., "The Economics of Reproduc- ibility in Preclinical Research," PLOS Biol. 13(6), (2015). 4. L.P. Freedman et al., "The culture of Cell Culture Practices and Authentication—Results from a 2015 Survey," BioTechniques 59(4), (2015). Cell Line Authentication Continued from page 23 Bioprocessing Insights Bioprocessing Ventria Bioscience said October 23, 2017 it won a $4.2 million grant from the Bill & Melinda Gates Foundation toward the biomanufacturing of new therapeutics targeting enterotoxigenic Escherichia coli (ETEC). Ventria said the grant will enable it to develop its ExpressTec technology platform for producing potential ETEC treatments. " This initiative aims to develop a new kind of oral treatment that could be delivered economically on a large scale for use in children or adults," Ventria President and CEO Scott E. Deeter said in a statement. ExpressTec is designed to produce recombinant proteins, small peptides, multisubunit molecules, monoclonal antibodies, fusion proteins, and enzymes used in medicine and biotechnol- ogy. Instead of using a stainless steel bioreactor, ExpressTec pro- teins are manufactured within a growing plant using sunlight for an energy source and soil, water, and air as raw materials. According to Ventria, ExpressTec offers several advantages compared to biomanufacturing with bacterial, yeast, and mammalian cell culture expression systems, transgenic ani- mals, or purification from natural sources. These advantages include higher product yields, the absence of contamination from components of animal or human origin, reduced carbon footprint from the manufacturing process, a "dramatically" lower cost of production, and a broadly flexible platform. Proteins produced through ExpressTec, Ventria adds, are free of animal, human, and bacterial contaminants; safer and more reliable than blood-derived products; and cost-effective. "We have proven the effectiveness of our ExpressTec system for biomanufacturing synthetic colostrum proteins, such as lactoferrin and lysozyme," Deeter added. "This new application in the global fight against ETEC adds to Ventria's pipeline of projects with the potential to make a real differ- ence in people's health." Doubling Production Capacity Ventria's grant from the Gates Foundation comes more than a month after the company broke ground on a $1.5 million, 3,000-square-foot addition to its biomanufacturing and labo- ratory facilities that the company said would roughly double its recombinant protein production capacity. Ventria is expanding its molecular biology lab, greenhouses, process development and analytical lab, and processing capacity in Junction City, KS, where the company is head- quartered. The grant also reflects one of the Foundation's funding priorities—initiatives intended to help reach the goal of ending diarrheal disease deaths in children under five years of age by 2030. ETEC accounted for an estimated 157,000 deaths per year—9% of all deaths attributed to diarrhea and approxi- mately 1% of all deaths in children 28 days to five years of age, according to the Global Burden of Disease 2010 study. The World Health Organization reported in 2006 that ETEC is the most common cause of diarrhea in the developing world, with an estimated 280 million to 400 million cases in children aged under 5 years and an additional 100 million episodes in children aged 5 to 14 years. "ETEC infection cries out for an effective treatment that can be delivered on a large scale in areas struggling with poverty, and the Gates Foundation initiative brings hope to patients and societies afflicted by this disease," added Ventria CMO Seymour Fein, M.D. n Ventria Wins $4.2M Gates Foundation Grant toward Biomanufacturing ETEC Therapeutics Fi g u re 4 . Th e rm o Fi s h e r S c i e nt i f i c s ays t h at w i t h t h e a d ve nt o f h i g h e r t h ro u g h p u t instrumentation and more robust amplification technology, laboratory bottlenecks have shifted from sample processing to data analysis. To expedite data review tasks, such as those related to genetic drift, the company has developed GeneMapper® software, which combines expert system and expert assistant capabilities. Developed and tested with your experiments in mind High-Quality Heat Shock Proteins Explore these and more than 50 Hsp inhibitors at Pure | Native | Full Length Available in Bulk

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