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  Together is better: mRNA Co-encapsulation in lipoplexes is required to obtain ratiometric Co-delivery and protein expression on the single cell level

Zhang, H., Bussmann, J., Huhnke, F. H., Devoldere, J., Minnaert, A.-K., Jiskoot, W., 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, 2102072, pp. 1-14. doi:10.1002/advs.202102072.

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 Creators:
Zhang, Heyang, Author
Bussmann, Jeroen, Author
Huhnke, Florian H.1, Author              
Devoldere, Joke, Author
Minnaert, An-Katrien, Author
Jiskoot, Wim, Author
Serwane, Friedhelm1, Author              
Spatz, Joachim P.1, Author              
Röding, Magnus, Author
Smedt, Stefaan C. De, Author
Braeckmans, Kevin, Author
Remaut, Katrien, Author
Affiliations:
1Cellular Biophysics, Max Planck Institute for Medical Research, Max Planck Society, ou_2364731              

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Free keywords: cellular uptake, mingle/single-mRNA lipoplex, protein expression, single cell, theoretical modeling
 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.

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Language(s): eng - English
 Dates: 2021-10-272021-05-182021-12-16
 Publication Status: Published online
 Pages: 14
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1002/advs.202102072
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Title: Advanced Science
  Other : Adv. Sci.
Source Genre: Journal
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Publ. Info: Weinheim : Wiley-VCH
Pages: - Volume / Issue: - Sequence Number: 2102072 Start / End Page: 1 - 14 Identifier: ISSN: 2198-3844
CoNE: https://pure.mpg.de/cone/journals/resource/2198-3844