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© Artur Scherf
Scanning Electron Microscopy of Red Blood Cell infected by Plasmodium falciparum.
Publication : Cell metabolism

Improving Drug Discovery by Nucleic Acid Delivery in Engineered Human Microlivers

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Cell metabolism - 05 Mar 2019

Mancio-Silva L, Fleming HE, Miller AB, Milstein S, Liebow A, Haslett P, Sepp-Lorenzino L, Bhatia SN

Link to Pubmed [PMID] – 30840913

Cell Metab. 2019 Mar;29(3):727-735.e3

The liver plays a central role in metabolism; however, xenobiotic metabolism variations between human hepatocytes and those in model organisms create challenges in establishing functional test beds to detect the potential drug toxicity and efficacy of candidate small molecules. In the emerging areas of RNA interference, viral gene therapy, and genome editing, more robust, long-lasting, and predictive human liver models may accelerate progress. Here, we apply a new modality to a previously established, functionally stable, multi-well bioengineered microliver-fabricated from primary human hepatocytes and supportive stromal cells-in order to advance both small molecule and nucleic acid therapeutic pipelines. Specifically, we achieve robust and durable gene silencing in vitro to tune the human metabolism of small molecules, and demonstrate its capacity to query the potential efficacy and/or toxicity of candidate therapeutics. Additionally, we apply this engineered platform to test siRNAs designed to target hepatocytes and impact human liver genetic and infectious diseases.

https://www.ncbi.nlm.nih.gov/pubmed/30840913