HIGH THROUGHPUT METHOD FOR SCREENING LIPID NANOPARTICLE EFFICACY AND CYTOTOXICITY
Researchers at Berkeley have developed synthetic cell membranes that are optimized for screening the toxicity and efficacy of lipid nanoparticle formulations in vitro, in a high throughput format.
Lipid nanoparticles (LNPs) represent a highly effective and efficient method for the delivery of macromolecules into cells in vivo and in vitro. Several commercially available therapeutics exist using LNPs, most notably the Moderna and Pfizer/BioNTech vaccines against SARS-CoV2. While these applications have proved clinically useful, the clinical use of LNPs is limited due to several caveats. Expanding the use of nucleic acid-based therapies for different indications hinges on the ability to continuously evolve the design of LNPs with high potency, better endosomal escape, cellular-specific targeting, and low toxicity. Despite this need, few screening platforms for LNP libraries exist.
Stage of Research
The inventors have developed a novel method for high throughput screening of LNP libraries. This screening method classifies LNP formulations based on cytotoxicity and effective endosomal escape, two important criteria for and LNP formulation’s efficacy in vivo. More specifically, this method employs synthetic cells that encapsulate a water-soluble fluorescent dye or whose membranes are labeled with a lipophilic fluorescent dye at self-quenching dye concentrations. These modifications allow these cells to be incubated with LNPs and provide a read out of LNP-induced membrane permeabilization and LNP- membrane fusion, which are proxies for LNP toxicity and efficacy respectively.
Applications
- Accurate assessment of LNP toxicity and efficacy to inform an LNP formulation’s use in vivo.
Advantages
- High throughput methodology that allows for the screening of many LNP formulations
- Eliminates trial and error in vivo, leading to fewer associated costs from failed formulations
Stage of Development
Research- in vitro
Publications
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Related Web Links
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Keywords
Nanoparticle, SARS-CoV2, vaccine
Technology Reference
CZ Biohub SF ref. no. CZB-286B
UC Berkeley ref. no. B23-134
