A Reverse Transcription Nucleic-Acid-Based Barcoding System for <i>In Vivo</i> Measurement of Lipid Nanoparticle mRNA Delivery

Lipid nanoparticles (LNPs) are the most extensively validated clinical delivery vehicles for mRNA therapeutics, exemplified by their widespread use in the mRNA COVID-19 vaccines. The pace of lipid nanoparticle (LNP) development for mRNA therapeutics is restricted by the limitations of existing methods for large-scale LNP screening. To address this challenge, we developed Quantitative Analysis of Reverse Transcribed Barcodes (QuART), a novel nucleic-acid-based system for measuring LNP functional delivery in vivo. QuART uses a bacterial retron reverse transcription system to couple functional mRNA delivery into the cytoplasm with a cDNA barcode readout. Our results demonstrate that QuART can be used to identify functional mRNA delivery both in vitro in cell culture and in vivo in mice. Multiplexing of QuART could enable high-throughput screening of LNP formulations, facilitating the rapid discovery of promising LNP candidates for mRNA therapeutics.

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Publication Details

Journal
ACS Bio & Med Chem Au
Published
2025-02-05
DOI
https://doi.org/10.1021/acsbiomedchemau.4c00081
Citations
2
Primary Topic
RNA Interference and Gene Delivery
Type
article
Field-Weighted Citation Impact
1.61

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article

A Reverse Transcription Nucleic-Acid-Based Barcoding System for In Vivo Measurement of Lipid Nanoparticle mRNA Delivery

Rick Xing Ze Lu, Basil P. Hubbard, Tiana L. Young, Ke Wang et al.
2 citations
ACS Bio & Med Chem Au
RNA Interference and Gene Delivery
1.61
article

A Reverse Transcription Nucleic-Acid-Based Barcoding System for In Vivo Measurement of Lipid Nanoparticle mRNA Delivery

Rick Xing Ze Lu, Basil P. Hubbard, Tiana L. Young, Ke Wang, Shannon J. Tsai, Fanglin Gong, Andrew Varley, Nicholas C. Solek, Bowen Li, Yue Xu, Jingan Chen
article en
2 citations

Abstract

Lipid nanoparticles (LNPs) are the most extensively validated clinical delivery vehicles for mRNA therapeutics, exemplified by their widespread use in the mRNA COVID-19 vaccines. The pace of lipid nanoparticle (LNP) development for mRNA therapeutics is restricted by the limitations of existing methods for large-scale LNP screening. To address this challenge, we developed Quantitative Analysis of Reverse Transcribed Barcodes (QuART), a novel nucleic-acid-based system for measuring LNP functional delivery in vivo. QuART uses a bacterial retron reverse transcription system to couple functional mRNA delivery into the cytoplasm with a cDNA barcode readout. Our results demonstrate that QuART can be used to identify functional mRNA delivery both in vitro in cell culture and in vivo in mice. Multiplexing of QuART could enable high-throughput screening of LNP formulations, facilitating the rapid discovery of promising LNP candidates for mRNA therapeutics.

ACS Bio & Med Chem AuVol. 5(1)
University Health Network (CA), 3M (United States) (US), University of Toronto (CA), Princess Margaret Cancer Centre (CA), Institute of Biomedical Science (GB)
University Health Network, J.P. Bickell Foundation, Canada Foundation for Innovation, Canada Research Chairs, University of Toronto, Connaught Fund, Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada
Openalex Percentile: Top 19%
RNA Interference and Gene Delivery
1.61
DOIOpen Access PDFOpenAlex
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