ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2022
Together is Better: mRNA Co-Encapsulation in Lipoplexes is Required to Obtain Ratiometric Co-Delivery and Protein Expression on the Single Cell Level.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Analysis of multi-drug cancer nanomedicine.Nature nanotechnology · 2025Pooled it
- A systematic review of nanocarriers used in medicine and beyond - definition and categorization framework.Journal of nanobiotechnology · 2025Pooled it
- Retinal Organoids from Induced Pluripotent Stem Cells of Patients with Inherited Retinal Diseases: A Systematic Review.Stem cell reviews and reports · 2025Pooled it
- Soaking Up Success: Sponge-Assisted Nanoparticle Transfection.Research square · 2026Article
- 3D Quantification of Viral Transduction Efficiency in Living Human Retinal Organoids.Small methods · 2026Article
- The design, manufacture and LNP formulation of mRNA for research use.Nature protocols · 2025Article
- Development of an in situ CAR-T cell protocol through optical and PSMA-targeted PET imaging.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Femtosecond laser-ablative aqueous synthesis of multi-drug antiviral nanoparticles.Nanomedicine (London, England) · 2025Article
- Less is more: slow-codon windows enhance eGFP mRNA resilience against RNA interference.Journal of the Royal Society, Interface · 2025Article
- Mechanistic insights into Sindbis virus infection: noncapped genomic RNAs enhance the translation of capped genomic RNAs to promote viral infectivity.Nucleic acids research · 2025Article
- Base editors in zebrafish: a new era for functional genomics and disease modeling.Frontiers in genome editing · 2025Review
- Advances in mRNA LNP-Based Cancer Vaccines: Mechanisms, Formulation Aspects, Challenges, and Future Directions.Journal of personalized medicine · 2024Review
- Transformative Impact of Nanocarrier-Mediated Drug Delivery: Overcoming Biological Barriers and Expanding Therapeutic Horizons.Small science · 2024Article
- Recent Research Advances in Nano-Based Drug Delivery Systems for Local Anesthetics.Drug design, development and therapy · 2023Review
- Current clinical status of new COVID-19 vaccines and immunotherapy.Environmental science and pollution research international · 2022Review
- Regulatory guidelines and preclinical tools to study the biodistribution of RNA therapeutics.Advanced drug delivery reviews · 2022Review
- 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 (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Recent advances in nano-drug delivery systems for synergistic antitumor immunotherapy.Frontiers in bioengineering and biotechnology · 2022Review
Corrections and comments
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Authors and funding
12 authors.
Funding
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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.