ASSESSMENT OF A MICROPATTERNED HEPATOCYTE CO-CULTURE SYSTEM TO DETECT COMPOUNDS THAT CAUSE DRUG INDUCED LIVER INJURY IN HUMANS
Poster Mar 13, 2012
Salman Khetani, Chitra Kanchagar, Stacy Krzyzewski, Michael D. Aleo and Yvonne Will
In vitro approaches which reliably predict in vivo human drug metabolite profiles are highly desired as a means to streamline drug development timelines and substantially reduce development costs. Major metabolites of many compounds can be predicted using traditional in vitro systems such as liver microsomes. The rates of success, however, are typically in the range of 50%. Thus, there is considerable room for improving in vitro systems for predicting human metabolite profiles. This case study demonstrates the increased success of Hepregen’s HepatoPac™ system in identifying primary and secondary circulating and excretory metabolites when compared to liver microsomes, S-9 fractions and primary human hepatocyte suspensions for a series of 27 compounds with known in vivo human metabolite profiles.
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We utilized paired synthetic crRNAs coupled with our synthetic tracrRNA in cells transduced with lentiviral Cas9 to perform a functional knockout on hsa-miR-221. This three-part system (crRNA, tracrRNA and Cas9) has demonstrated efficient gene editing when used with only one guide RNA, but the goal was to use two crRNAs to remove the entire stem-loop.READ MORE