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Together is Better :
Together is Better : mRNA Co-Encapsulation in Lipoplexes is Required to Obtain Ratiometric Co-Delivery and Protein Expression on the Single Cell Level
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- Zhang, Heyang (author)
- Ghent University, Belgium,Universiteit Gent,Ghent university
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- Bussmann, Jeroen (author)
- Leiden University, Netherlands,Universiteit Leiden (UL),Leiden University (UL)
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- Huhnke, Florian (author)
- Max Planck Institute for Medical Research, Germany,Max Planck Gesellschaft zur Förderung der Wissenschaften e.V. (MPG),Max Planck Society for the Advancement of Science (MPG)
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- Devoldere, Joke (author)
- Ghent University, Belgium,Universiteit Gent,Ghent university
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- Minnaert, An-Katrien (author)
- Ghent University, Belgium,Universiteit Gent,Ghent university
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- Jiskoot, Wim (author)
- Leiden University, Netherlands,Universiteit Leiden (UL),Leiden University (UL)
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- Serwane, Friedhelm (author)
- Max Planck Institute for Medical Research, Germany; Ludwig-Maximilian-University Munich, Germany; Munich Cluster for Systems Neurology, Germany,Ludwig-Maximilians-Universität München,Ludwig Maximilian University of Munich,Max Planck Gesellschaft zur Förderung der Wissenschaften e.V. (MPG),Max Planck Society for the Advancement of Science (MPG)
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- Spatz, Joachim (author)
- Max Planck Institute for Medical Research, Germany; University of Heidelberg, Germany,Ruprecht-Karls-Universität Heidelberg,Heidelberg University,Max Planck Gesellschaft zur Förderung der Wissenschaften e.V. (MPG),Max Planck Society for the Advancement of Science (MPG)
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- Röding, Magnus (author)
- Gothenburg University,Göteborgs universitet,RISE,Jordbruk och livsmedel,Chalmers University of Technology, Sweden; University of Gothenburg, Sweden,RISE Research Institutes of Sweden,Chalmers tekniska högskola,Institutionen för matematiska vetenskaper,Department of Mathematical Sciences
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- De Smedt, Stefaan (author)
- Ghent University, Belgium,Universiteit Gent,Ghent university
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- Braeckmans, Kevin (author)
- Ghent University, Belgium,Universiteit Gent,Ghent university
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- Remaut, Katrien (author)
- Ghent University, Belgium,Universiteit Gent,Ghent university
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(creator_code:org_t)
- 2021-12-16
- 2022
- English.
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In: Advanced Science. - : John Wiley and Sons Inc. - 2198-3844. ; 9:4
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Abstract
Subject headings
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- 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. © 2021 The Authors.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Utvecklingsbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Developmental Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- cellular uptake
- mingle/single-mRNA lipoplex
- protein expression
- single cell
- theoretical modeling
- Cells
- Cytology
- Encoding (symbols)
- Proteins
- RNA
- Signal encoding
- Individual cells
- Lipoplexes
- Messenger RNA
- Mingle/single-messenger RNA lipoplex
- Protein expressions
- Ratiometric
- Single cells
- Single-cell level
- Liposomes
- cellular uptake
- mingle
- single-mRNA lipoplex
- protein expression
- single cell
- theoretical modeling
- mediated delivery
- endosomal escape
- sirna
- integrity
- polyplex
- vaccine
- Chemistry
- Science & Technology - Other Topics
- Materials Science
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
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Zhang, Heyang
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Bussmann, Jeroen
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Huhnke, Florian
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Devoldere, Joke
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Minnaert, An-Kat ...
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Jiskoot, Wim
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show more...
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Serwane, Friedhe ...
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Spatz, Joachim
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Röding, Magnus
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De Smedt, Stefaa ...
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Braeckmans, Kevi ...
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Remaut, Katrien
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Cell Biology
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Developmental Bi ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
- Articles in the publication
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Advanced Science
- By the university
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RISE
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Chalmers University of Technology
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University of Gothenburg