Development of a disposable cell-free ion channel measurement platform for hERG s

DESCRIPTION (provided by applicant): Assaying ion channels for pharmaceutical discovery and safety screening is problematic to perform in high throughput because the ion channels must be incorporated into a cell membrane to allow measurement of their ionictransport to determine their functionality. As a result, there are currently no high quality, high throughput assays for ion channel screening. Recent developments of automated patch clamp instrumentation are still over an order of magnitude lower throughput than conventional drug screening for soluble proteins and also require expensive instrumentation, specialized cell lines, and consumables. For existing methods of ion channel screening, there is a large gap in information quality, throughput, and cost.Librede Inc. is developing an alternative cell-free technology for ion channel screening using artificial cell membranes. Librede's patent pending formulation of cell-free artificial membranes can enable higher throughput and lower consumable costs whilerequiring less expensive equipment and trained personnel. Librede was founded by UCLA researchers and the inventors of this technology. In the work proposed here, we aim to develop materials and methods for measurement and packaging of the hERG channel inour artificial membrane platform. hERG is an important ion channel to screen, since off-target activity of pharmaceuticals on the hERG channel can lead to cardiac arrhythmia and death; thus all drug candidates, irrespective of target, must be screened against interaction with hERG. For this work, we will collaborate with the Schmidt group at UCLA, who has demonstrated the measurement of hERG in artificial membranes in preliminary work, a first. We aim to determine the compatibility of hERG with Librede's artificial membrane platform and determine the conditions with optimize the long term storage of hERG packaged with our membrane array plates. Finally, we will perform a demonstration of our technology by screening hERG against known channel blockers over a48 membrane array plate simultaneously. This work is a key step toward our goal of reducing the cost and expertise required for ion channel screening. PUBLIC HEALTH RELEVANCE: We have recently developed a novel ion channel measurement platform thatmay be indefinitely stored, commercially shipped, and requires very little input from the end user to operate. We aim to validate this platform with the human cardiac ion channel hERG to demonstrate the utility of this technology for ion channel screening.