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Technology Development Initiative – Paper of the Month – December 2022

A figure from this study.

Image copyright – Nature.

Nanoparticle single-cell multiomic readouts reveal that cell heterogeneity influences lipid nanoparticle-mediated messenger RNA delivery

Published in Nature Nanotechnology.

Authors

Curtis Dobrowolski, Kalina Paunovska, Elisa Schrader Echeverri, David Loughrey, Alejandro J. Da Silva Sanchez, Huanzhen Ni, Marine Z. C. Hatit, Melissa P. Lokugamage, Yanina Kuzminich, Hannah E. Peck, Philip J. Santangelo & James E. Dahlman

Paper presented by Dr. Atul Daiwile and selected by the NIDA TDI Paper of the Month Committee

Background and Technological Advancement

Cells within tissues can be described as homogeneous but are composed of subsets of cells with distinct transcriptional states that may influence their ability to undergo gene transfer by nanoparticles. To test this hypothesis, researchers from the Georgia Institute of Technology and Emory University’s School of Medicine have developed a system that makes nanoparticle delivery to subsets of cells more predictable by combining DNA barcoding with a nanoparticle delivery system called single-cell nanoparticle targeting-sequencing (SENT-seq). Using SENT-seq, the investigators identified how different nanoparticles deliver DNA barcodes and mRNA into cells to affect the transcriptome and proteome with single cell resolution. They also identified cell subtypes that exhibit relatively high and low nanoparticle uptake in a heterogeneous cell population which has not been previously possible using conventional techniques.


Dobrowolski, Curtis; Paunovska, Kalina; Echeverri, Elisa Schrader; Loughrey, David; Sanchez, Alejandro J Da Silva; Ni, Huanzhen; Hatit, Marine Z C; Lokugamage, Melissa P; Kuzminich, Yanina; Peck, Hannah E; Santangelo, Philip J; Dahlman, James E

Nanoparticle single-cell multiomic readouts reveal that cell heterogeneity influences lipid nanoparticle-mediated messenger RNA delivery Journal Article

In: Nat Nanotechnol, vol. 17, no. 8, pp. 871–879, 2022, ISSN: 1748-3395.

Abstract | Links

@article{pmid35768613,
title = {Nanoparticle single-cell multiomic readouts reveal that cell heterogeneity influences lipid nanoparticle-mediated messenger RNA delivery},
author = {Curtis Dobrowolski and Kalina Paunovska and Elisa Schrader Echeverri and David Loughrey and Alejandro J Da Silva Sanchez and Huanzhen Ni and Marine Z C Hatit and Melissa P Lokugamage and Yanina Kuzminich and Hannah E Peck and Philip J Santangelo and James E Dahlman},
url = {https://pubmed.ncbi.nlm.nih.gov/35768613/},
doi = {10.1038/s41565-022-01146-9},
issn = {1748-3395},
year = {2022},
date = {2022-08-01},
urldate = {2022-08-01},
journal = {Nat Nanotechnol},
volume = {17},
number = {8},
pages = {871--879},
abstract = {Cells that were previously described as homogeneous are composed of subsets with distinct transcriptional states. However, it remains unclear whether this cell heterogeneity influences the efficiency with which lipid nanoparticles (LNPs) deliver messenger RNA therapies in vivo. To test the hypothesis that cell heterogeneity influences LNP-mediated mRNA delivery, we report here a new multiomic nanoparticle delivery system called single-cell nanoparticle targeting-sequencing (SENT-seq). SENT-seq quantifies how dozens of LNPs deliver DNA barcodes and mRNA into cells, the subsequent protein production and the transcriptome, with single-cell resolution. Using SENT-seq, we have identified cell subtypes that exhibit particularly high or low LNP uptake as well as genes associated with those subtypes. The data suggest that cell subsets have distinct responses to LNPs that may affect mRNA therapies.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

Close

Cells that were previously described as homogeneous are composed of subsets with distinct transcriptional states. However, it remains unclear whether this cell heterogeneity influences the efficiency with which lipid nanoparticles (LNPs) deliver messenger RNA therapies in vivo. To test the hypothesis that cell heterogeneity influences LNP-mediated mRNA delivery, we report here a new multiomic nanoparticle delivery system called single-cell nanoparticle targeting-sequencing (SENT-seq). SENT-seq quantifies how dozens of LNPs deliver DNA barcodes and mRNA into cells, the subsequent protein production and the transcriptome, with single-cell resolution. Using SENT-seq, we have identified cell subtypes that exhibit particularly high or low LNP uptake as well as genes associated with those subtypes. The data suggest that cell subsets have distinct responses to LNPs that may affect mRNA therapies.

Close

  • https://pubmed.ncbi.nlm.nih.gov/35768613/
  • doi:10.1038/s41565-022-01146-9

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