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DNA-Directed Patterning for Versatile Validation and Characterization of a Lipid-Based Nanoparticle Model of SARS-CoV-2

submitted on 12.03.2021, 17:46 and posted on 16.03.2021, 05:37 by Molly Kozminsky, Thomas Carey, Lydia L. Sohn
Lipid-based nanoparticles have risen to the forefront of the COVID-19 pandemic—from encapsulation of vaccine components to modeling the virus, itself. Their rapid development in the face of the volatile nature of the pandemic requires high-throughput, highly flexible methods for characterization. DNA-directed patterning is a versatile method to immobilize and segregate lipid-based nanoparticles for subsequent analysis. DNA-directed patterning selectively conjugates oligonucleotides onto a glass substrate and then hybridizes them to complementary oligonucleotides tagged to the liposomes, thereby patterning them with great control and precision. The power of this method is demonstrated by characterizing a novel recapitulative lipid-based nanoparticle model of SARS-CoV-2 —S-liposomes— which present the SARS-CoV-2 spike (S) protein on their surfaces. Patterning of a mixture of S-liposomes and liposomes that display the tetraspanin CD63 into discrete regions of a substrate is used to show that ACE2 specifically binds to S-liposomes. Importantly, DNA-directed patterning of S-liposomes is used to verify the performance of a commercially available neutralizing antibody against the S protein. Ultimately, the introduction of S-liposomes to ACE2-expressing cells demonstrates the biological relevance of DNA-directed patterning. Overall, DNA-directed patterning enables a wide variety of custom assays for the characterization of any lipid-based nanoparticle.


CITRIS COVID 19 Response Seed Funding

DNA-Directed Micropatterning of Cells to Investigate Prostate Cancer Dormancy in the Bone Marrow

National Cancer Institute

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University of California Cancer Research Coordinating Committee Fellowship

Michael and Margaret Checca


Email Address of Submitting Author


University of California, Berkeley


United States

ORCID For Submitting Author


Declaration of Conflict of Interest

M Kozminsky, TR Carey, and LL Sohn have filed a patent (PCT/US20/62957) that includes DNA labeling and patterning of S-liposomes.