Tools for drug efficacy studies in perfused tissue models - ¿
DESCRIPTION (provided by applicant): Organ-on-a-chip tools that recapitulate human biology, physiology and pathology are critically needed in basic and applied science research, toxicology, and drug lead development to, ultimately, extend and improve the quality of life by advancing knowledge and expediting discovery while reducing research costs and animal sacrifice. Unfortunately, most products incorporating circulation mimicking perfusion are too complicated for researchers to use, incompatible with many protocols and reads, and low-throughput. Our goal is to change this for ordinary lab personnel and for researchers across disciplines. We will make a researcher-centric product which does not require special skills or training for use, a tool that is flexible enough to serve diverse research objectives, and a tool which for pharmaceutical industry means a simple, low-cost platform for more predictive, multiplexed testing of drugs and drug combination strategies. Lena Biosciences' organs-on-a-chip will comprise artificial vasculature and be in a standard, screening- accessible format known to any user in life sciences, biotechnology and drug discovery for ease of use and user adoption. This platform will support vascularized 3D organ models for physiologically closer drug delivery and distribution by mimicking vasculature-to-tissue resistance and intra-tissue resistance to drug transport. It will be especially well suited for in vitro testing of humanized, high molecular weight therapeutics which are administered to patients intravenously and retained in circulation for the period of weeks. The platform will further provide concentrated cel secretome, proteome, metabolome, degradome, interactome etc. to facilitate detection and identification of biomarkers of therapeutic efficacy, cellular and biochemical changes in response to drugs and other stimuli, and therefore serve as a diagnostic and prognostic research tool in order to, for example, prevent serious reactions in clinical trials. Next, this organ-on-a-chip tool will also lend itself useful for development of de novo drug resistant tissue clones. The acquired-drug-resistance tissue clones will enable testing of new drug combinations that are critically needed for approved frontline therapy drugs on which patients eventually relapse. Lastly, this platform will be in sufficient throughput, compliant with most protocols, assays, reads and imaging setups researchers use routinely, and have zero dead volume to minimize use of expensive developmental drugs. The platform utility will be demonstrated using 3D models of liver, brain and breast cancer, and further validated by demonstrating in vitro testing of drugs and their combinations.