Genetic Engineering & Biotechnology News

APR15 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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Genetic Engineering & Biotechnology News | | APRIL 15, 2017 | 9 gan-level assessments of drug-induced liver injury, then delves more deeply, assessing cel- lular mechanisms, "when that is necessary to explain the liver injury." The DILISym model also has three sub- models outlining the major pathways by which a drug may cause liver injury. These are via oxidative stress, interference with mi- tochondrial function, and alterations in bile acid homeostasis. Partner companies quanti- tatively test drugs on these pathways in the laboratory and directly plug the results into DILISym, thus expanding the database. The DILISym software can then be used to test drug compounds in various simulated popu- lations, or "SimPops." Individuals within this database can ex- press a wide range of responses to the com- pounds in question, allowing for population variability in genetic, disease, and environ- mental factors. DILISym has also been ex- panded to simulate liver damage in Beagle dogs, Sprague-Dawley rats, and C57BL/6 mice. It doesn't hurt that DILISym model- ing has already been presented in regulatory submissions including a recent NDA. Body-on-a-Chip Devices On the other end of the spectrum is a more personal approach. A collaboration between James Hickman, Ph.D., head of the Hybrid Systems Lab at the University of Central Florida, and Michael Shuler, Ph.D., professor of chemical and biomolecular en- gineering at Cornell University, focuses on the development of body-on-a-chip devices, microfluidic platforms that contain several compartments, each of which corresponds to a different organ. Each compartment con- tains cell cultures derived from the same individual. What makes the body-on-a-chip device even more fascinating is its ability to circu- late media between all the different compart- ments. The device uses a pumpless rocker platform, which induces a gravity flow that also keeps the shear stress on the cells within acceptable physiological ranges. By simulat- ing circulation, the device allows for the eval- uation of multiorgan toxicity in response to any potential developing drug. "It is important to note that the medium is serum-free, cutting down on the variability that would normally be associated with hav- ing animal serum," says Dr. Hickman. "This in turn improves upon the ability to predict drug efficacy with more accuracy." Drs. Hickman and Shuler have established a four-organ chip using cardiac, liver, skel- etal, and neuronal cultures, and they have maintained these cultures over the course of 14 days in the aforementioned serum-free media. They are also working on expanding their platform, including maintaining 10 dif- ferent organs on the same chip. A device with such capabilities would en- able groundbreaking advances in personal- ized healthcare. Cultures of cells from a dis- eased individual's organs or derived from in- duced pluripotent stem cells could be main- tained on the chip and treated with multiple drugs. Then, drugs identified as curative and nontoxic could be administered to the pa- tient without fear of any adverse effects. The body-on-a-chip approach to drug evaluation could be even more valuable in treating pa- tients who suffer from rare diseases. Drs. Hickman and Shuler have founded a company called Hesperos that will specialize in developing body-on-a-chip technology for toxicological and efficacy testing. The com- ©2016 All rights reserved Mirus Bio LLC. Mirus Bio and TransIT are registered trademarks of Mirus Bio LLC. All trademarks are the property of their respective owners. Delivery by X2 X2 X2 siRNA DNA Functional Co-delivery of Plasmid DNA and siRNA. TransIT-X2 ® Dynamic Delivery System was used to simultaneously transfect Cy™5-labeled plasmid DNA (blue) encoding nuclear YFP (yellow) and Cy™3-labeled siRNA (red) into HeLa cells. Actin cytoskeleton is stained green. Visit for full experimental details. Achieve superior transfections with an advanced non-liposomal, polymeric system that effi ciently delivers DNA and/or RNA out of the endosome and into the cytoplasm, overcoming a critical barrier to nucleic acid delivery. The TransIT-X2 ® Dynamic Delivery System gives researchers: Efficiency–superior broad spectrum transfection Delivery–independent or simultaneous delivery of plasmid DNA and siRNA Technology–novel, non-liposomal, polymeric technology X2 X2 X2 ADVANCE YOUR TRANSFECTIONS. Request a FREE SAMPLE of TransIT-X2 ® Dynamic Delivery System. Visit, call 888.530.0801 (U.S. only) or +1.608.441.2852 (outside the U.S.) TransIT-X2 ® Dynamic Delivery System See Drug Toxicity on page 10 Drug Discovery A huge challenge in predicting drug efficacy and toxicity is progressing from in vitro tests to animal models.

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