Together is better : mRNA co‐encapsulation in lipoplexes is required to obtain ratiometric co‐delivery and protein expression on the single cell level
- Author
- Heyang Zhang, Jeroen Bussmann, Florian H. Huhnke, Joke Devoldere (UGent) , An-Katrien Minnaert (UGent) , Wim Jiskoot, Friedhelm Serwane, Joachim Spatz, Magnus Röding, Stefaan De Smedt (UGent) , Kevin Braeckmans (UGent) and Katrien Remaut (UGent)
- Organization
- Project
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- NANOBUBBLE (Laser-induced vapour nanobubbles for intracellular delivery of nanomaterials and treatment of biofilm infections)
- The barrier role of the vitreoretinal interface toward intravitreal injected proteins, viruses and siRNA nanoparticles: ex vivo bovine screening models and siRNA nanoparticle design.
- DeLNAM (Strengthening the Research Area of Delivery of Nucleic acid mimics (NAMS) into bacteria to fight the antibiotic crisis)
- Abstract
- Liposomes can efficiently deliver messenger RNA (mRNA) into cells. When mRNA cocktails encoding different proteins are needed, a considerable challenge is to efficiently deliver all mRNAs into the cytosol of each individual cell. In this work, two methods are explored to co-deliver varying ratiometric doses of mRNA encoding red (R) or green (G) fluorescent proteins and it is found that packaging mRNAs into the same lipoplexes (mingle-lipoplexes) is crucial to efficiently deliver multiple mRNA types into the cytosol of individual cells according to the pre-defined ratio. A mixture of lipoplexes containing only one mRNA type (single-lipoplexes), however, seem to follow the "first come - first serve" principle, resulting in a large variation of R/G uptake and expression levels for individual cells leading to ratiometric dosing only on the population level, but rarely on the single-cell level. These experimental observations are quantitatively explained by a theoretical framework based on the stochasticity of mRNA uptake in cells and endosomal escape of mingle- and single-lipoplexes, respectively. Furthermore, the findings are confirmed in 3D retinal organoids and zebrafish embryos, where mingle-lipoplexes outperformed single-lipoplexes to reliably bring both mRNA types into single cells. This benefits applications that require a strict control of protein expression in individual cells.
- Keywords
- cellular uptake, mingle, single-mRNA lipoplex, protein expression, single cell, theoretical modeling, MEDIATED DELIVERY, ENDOSOMAL ESCAPE, SIRNA, INTEGRITY, POLYPLEX, VACCINE
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Advanced Science - 2021 - Zhang - Together is Better mRNA Co Encapsulation in Lipoplexes is Required to Obtain Ratiometric.pdf
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-8742464
- MLA
- Zhang, Heyang, et al. “Together Is Better : MRNA Co‐encapsulation in Lipoplexes Is Required to Obtain Ratiometric Co‐delivery and Protein Expression on the Single Cell Level.” ADVANCED SCIENCE, vol. 9, no. 4, 2021, doi:10.1002/advs.202102072.
- APA
- Zhang, H., Bussmann, J., Huhnke, F. H., Devoldere, J., Minnaert, A.-K., Jiskoot, W., … Remaut, K. (2021). Together is better : mRNA co‐encapsulation in lipoplexes is required to obtain ratiometric co‐delivery and protein expression on the single cell level. ADVANCED SCIENCE, 9(4). https://doi.org/10.1002/advs.202102072
- Chicago author-date
- Zhang, Heyang, Jeroen Bussmann, Florian H. Huhnke, Joke Devoldere, An-Katrien Minnaert, Wim Jiskoot, Friedhelm Serwane, et al. 2021. “Together Is Better : MRNA Co‐encapsulation in Lipoplexes Is Required to Obtain Ratiometric Co‐delivery and Protein Expression on the Single Cell Level.” ADVANCED SCIENCE 9 (4). https://doi.org/10.1002/advs.202102072.
- Chicago author-date (all authors)
- Zhang, Heyang, Jeroen Bussmann, Florian H. Huhnke, Joke Devoldere, An-Katrien Minnaert, Wim Jiskoot, Friedhelm Serwane, Joachim Spatz, Magnus Röding, Stefaan De Smedt, Kevin Braeckmans, and Katrien Remaut. 2021. “Together Is Better : MRNA Co‐encapsulation in Lipoplexes Is Required to Obtain Ratiometric Co‐delivery and Protein Expression on the Single Cell Level.” ADVANCED SCIENCE 9 (4). doi:10.1002/advs.202102072.
- Vancouver
- 1.Zhang H, Bussmann J, Huhnke FH, Devoldere J, Minnaert A-K, Jiskoot W, et al. Together is better : mRNA co‐encapsulation in lipoplexes is required to obtain ratiometric co‐delivery and protein expression on the single cell level. ADVANCED SCIENCE. 2021;9(4).
- IEEE
- [1]H. Zhang et al., “Together is better : mRNA co‐encapsulation in lipoplexes is required to obtain ratiometric co‐delivery and protein expression on the single cell level,” ADVANCED SCIENCE, vol. 9, no. 4, 2021.
@article{8742464,
abstract = {{Liposomes can efficiently deliver messenger RNA (mRNA) into cells. When mRNA cocktails encoding different proteins are needed, a considerable challenge is to efficiently deliver all mRNAs into the cytosol of each individual cell. In this work, two methods are explored to co-deliver varying ratiometric doses of mRNA encoding red (R) or green (G) fluorescent proteins and it is found that packaging mRNAs into the same lipoplexes (mingle-lipoplexes) is crucial to efficiently deliver multiple mRNA types into the cytosol of individual cells according to the pre-defined ratio. A mixture of lipoplexes containing only one mRNA type (single-lipoplexes), however, seem to follow the "first come - first serve" principle, resulting in a large variation of R/G uptake and expression levels for individual cells leading to ratiometric dosing only on the population level, but rarely on the single-cell level. These experimental observations are quantitatively explained by a theoretical framework based on the stochasticity of mRNA uptake in cells and endosomal escape of mingle- and single-lipoplexes, respectively. Furthermore, the findings are confirmed in 3D retinal organoids and zebrafish embryos, where mingle-lipoplexes outperformed single-lipoplexes to reliably bring both mRNA types into single cells. This benefits applications that require a strict control of protein expression in individual cells.}},
articleno = {{2102072}},
author = {{Zhang, Heyang and Bussmann, Jeroen and Huhnke, Florian H. and Devoldere, Joke and Minnaert, An-Katrien and Jiskoot, Wim and Serwane, Friedhelm and Spatz, Joachim and Röding, Magnus and De Smedt, Stefaan and Braeckmans, Kevin and Remaut, Katrien}},
issn = {{2198-3844}},
journal = {{ADVANCED SCIENCE}},
keywords = {{cellular uptake,mingle,single-mRNA lipoplex,protein expression,single cell,theoretical modeling,MEDIATED DELIVERY,ENDOSOMAL ESCAPE,SIRNA,INTEGRITY,POLYPLEX,VACCINE}},
language = {{eng}},
number = {{4}},
pages = {{14}},
title = {{Together is better : mRNA co‐encapsulation in lipoplexes is required to obtain ratiometric co‐delivery and protein expression on the single cell level}},
url = {{http://dx.doi.org/10.1002/advs.202102072}},
volume = {{9}},
year = {{2021}},
}
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