SubsidieMeestersQuantitative analysis of endosomal escape and intracellular delivery via bioorthogonal luminescent reaction
BioLure aims to revolutionize intracellular delivery quantification using a bioorthogonal luminescent reaction for high-throughput assessment of endosomal escape in live cells.
Projectdetails
Introduction
Intracellular delivery of membrane-impermeable biomacromolecules is essential for a broad spectrum of life sciences, ranging from fundamental biological studies to applied biomedical and pharmaceutical sciences. Despite the great efforts in developing new intracellular delivery nanocarriers in the recent 20 years, simple, high-throughput, and accurate intracellular delivery quantification in live cells is still technically challenging.
Proposed Method
In BioLure, I propose an unconventional approach to quantify intracellular delivery and endosomal escape by a bioorthogonal luminescent reaction in live cells. Instead of a bulky fluorophore, I will label the molecule of interest (MOI) to be delivered with a single amino acid tag, which causes minimal changes in MOI’s physicochemical properties and functions.
Mechanism of Action
The tag will generate luciferase substrate inside live cells upon successful translocation into the cytoplasm by bioorthogonal reactions with:
- Chemoselectivity
- Rapid kinetics
- Biocompatibility
- High efficiency
Application and Validation
The quantification strategy will initially be applied to the intracellular delivery of proteins via physical membrane disruption and validated by complementary methods. It will then be expanded to nanocarrier-mediated endosomal escape with different MOIs, including therapeutic siRNAs. The successful endosomal escape quantification will allow further nanoparticle screening for siRNA delivery.
Vision and Impact
I envision that BioLure will lead to a paradigm shift in the intracellular delivery field, facilitating the transformation from qualitative routine fluorescence imaging to high-throughput real-time quantification.
Benefits for Research
The high sensitivity and low background make it an appealing tool for:
- Biologists to study endosomal escape
- Material scientists to develop potent next-generation non-viral intracellular nanocarriers
Ultimately, it will facilitate the design and screening of endosomal escape carriers and future nanomedicine formulations.
Financiële details & Tijdlijn
Financiële details
| Subsidiebedrag | € 1.488.074 |
| Totale projectbegroting | € 1.488.074 |
Tijdlijn
| Startdatum | 1-1-2024 |
| Einddatum | 31-12-2028 |
| Subsidiejaar | 2024 |
Partners & Locaties
Projectpartners
- HELSINGIN YLIOPISTOpenvoerder
Land(en)
Vergelijkbare projecten binnen European Research Council
| Project | Regeling | Bedrag | Jaar | Actie |
|---|---|---|---|---|
MANUNKIND: Determinants and Dynamics of Collaborative ExploitationThis project aims to develop a game theoretic framework to analyze the psychological and strategic dynamics of collaborative exploitation, informing policies to combat modern slavery. | ERC STG | € 1.497.749 | 2022 | Details |
Elucidating the phenotypic convergence of proliferation reduction under growth-induced pressureThe UnderPressure project aims to investigate how mechanical constraints from 3D crowding affect cell proliferation and signaling in various organisms, with potential applications in reducing cancer chemoresistance. | ERC STG | € 1.498.280 | 2022 | Details |
The Ethics of Loneliness and SociabilityThis project aims to develop a normative theory of loneliness by analyzing ethical responsibilities of individuals and societies to prevent and alleviate loneliness, establishing a new philosophical sub-field. | ERC STG | € 1.025.860 | 2023 | Details |
Uncovering the mechanisms of action of an antiviral bacteriumThis project aims to uncover the mechanisms behind Wolbachia's antiviral protection in insects and develop tools for studying symbiont gene function. | ERC STG | € 1.500.000 | 2023 | Details |
MANUNKIND: Determinants and Dynamics of Collaborative Exploitation
This project aims to develop a game theoretic framework to analyze the psychological and strategic dynamics of collaborative exploitation, informing policies to combat modern slavery.
Elucidating the phenotypic convergence of proliferation reduction under growth-induced pressure
The UnderPressure project aims to investigate how mechanical constraints from 3D crowding affect cell proliferation and signaling in various organisms, with potential applications in reducing cancer chemoresistance.
The Ethics of Loneliness and Sociability
This project aims to develop a normative theory of loneliness by analyzing ethical responsibilities of individuals and societies to prevent and alleviate loneliness, establishing a new philosophical sub-field.
Uncovering the mechanisms of action of an antiviral bacterium
This project aims to uncover the mechanisms behind Wolbachia's antiviral protection in insects and develop tools for studying symbiont gene function.
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Versatile Amplification Method for Single-Molecule Detection in Liquid BiopsyVerSiLiB aims to develop an enzyme-free amplification platform for detecting proteins and nucleic acids in liquid biopsies, enhancing cancer management through novel affinity-mediated transport. | EIC Pathfinder | € 2.994.244 | 2022 | Details |
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Functional Nanoscale TherapeuticsDevelop functional hybrid nanoscale medicines to enhance intracellular delivery of mRNA and combat nanoscale pathogens, aiming for advanced therapies against diseases like cancer. | ERC ADG | € 2.499.796 | 2024 | Details |
Time-based single molecule nanolocalization for live cell imagingThe project aims to develop a novel live-cell nanoscopy technique that enables high-speed, high-resolution imaging of biological processes at the nanoscale without compromising depth or volume. | ERC ADG | € 2.498.196 | 2023 | Details |
Versatile Amplification Method for Single-Molecule Detection in Liquid Biopsy
VerSiLiB aims to develop an enzyme-free amplification platform for detecting proteins and nucleic acids in liquid biopsies, enhancing cancer management through novel affinity-mediated transport.
Linker molecules convert commercial fluorophores into tailored functional probes during biolabeling
The project aims to enhance the performance of fluorescent probes by developing versatile linker compounds that improve labeling properties for biomedical applications, reducing costs and increasing reliability.
Functional Nanoscale Therapeutics
Develop functional hybrid nanoscale medicines to enhance intracellular delivery of mRNA and combat nanoscale pathogens, aiming for advanced therapies against diseases like cancer.
Time-based single molecule nanolocalization for live cell imaging
The project aims to develop a novel live-cell nanoscopy technique that enables high-speed, high-resolution imaging of biological processes at the nanoscale without compromising depth or volume.