Cytosolic Protein Delivery Using Modular Biotin-Streptavidin Assembly of Nanocomposites
David C Luther1, Yi-Wei Lee1, Harini Nagaraj1
1Department of Chemistry, University of Massachusetts Amherst, 710 North Pleasant Street, Amherst, Massachusetts 01003, United States.
ACS Nano
|April 18, 2022
Summary
This study introduces a novel biotin-streptavidin method for efficient protein delivery into cells, bypassing endosomal entrapment. This versatile nanovector platform ensures protein cargo reaches the cytosol intact and functional.
Area of Science:
- Biotechnology
- Cell Biology
- Materials Science
Background:
- Protein delivery into cells is hindered by endosomal entrapment and degradation.
- Cytosolic delivery is crucial for therapeutic protein efficacy.
Purpose of the Study:
- To develop a modular nanovector system for efficient cytosolic delivery of biotinylated proteins.
- To overcome current limitations in protein delivery strategies.
Main Methods:
- Utilized biotin-streptavidin tethering to assemble biotinylated proteins and peptides.
- Formed polymer-protein nanocomposites via electrostatic self-assembly with cationic polymers.
- Evaluated delivery efficiency and protein function in cellular assays.
Main Results:
- Demonstrated efficient cytosolic delivery of six different biotinylated proteins.
- Confirmed retention of protein function through successful cell killing with granzyme A.
- Showcased the modularity and versatility of the nanovector platform.
Conclusions:
- The biotin-streptavidin tethering strategy provides a robust and modular approach for intracellular protein delivery.
- This platform enables the noncovalent assembly of delivery vectors for various protein cargos.
- The developed nanovectors facilitate direct cytosolic access, preserving protein integrity and function.
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