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A pH-sensitive eosin-block copolymer delivers proteins intracellularly.
Sören Reinhard1, Hesong Han, Jan Tuma
1Department of Bioengineering, University of California, and the Innovative Genomics Institute, 2151 Berkeley Way, Berkeley CA, 94720, USA. nmurthy@berkeley.edu.
Chemical Communications (Cambridge, England)
|October 28, 2020
Summary
A novel PEG-poly-eosin (PEG-pEosin) copolymer efficiently delivers active proteins into cells. This protein delivery system successfully enabled gene editing in cells and mouse brains.
Area of Science:
- Biotechnology
- Cell Biology
- Neuroscience
Background:
- Developing effective protein delivery methods into the cell cytoplasm is crucial for various therapeutic applications.
- Existing protein delivery systems often face challenges with protein stability and targeted release.
Purpose of the Study:
- To develop and evaluate a novel block copolymer for protein encapsulation and release.
- To assess the efficacy of this system for gene editing applications in vitro and in vivo.
Main Methods:
- Synthesis of a polyethylene glycol-poly-eosin (PEG-pEosin) block copolymer.
- Encapsulation of proteins, including Cre recombinase and listeriolysin O (LLO).
- Assessment of protein release under mildly acidic conditions and evaluation of gene editing efficiency in cell cultures and mouse brains following intracranial injection.
Main Results:
- The PEG-pEosin copolymer successfully encapsulated proteins, maintaining their activity upon release under mildly acidic conditions.
- A formulation containing Cre and LLO demonstrated efficient gene editing in cellular models.
- Intracranial injection of the PEG-pEosin formulation resulted in effective gene editing within the brains of mice.
Conclusions:
- PEG-pEosin represents a promising platform for the cytoplasmic delivery of functional proteins.
- This delivery system holds potential for advancing gene editing therapies and other protein-based interventions in both cellular and in vivo models, including the central nervous system.
