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Related Experiment Video

Updated: Apr 12, 2026

Rapid, Scalable Assembly and Loading of Bioactive Proteins and Immunostimulants into Diverse Synthetic Nanocarriers Via Flash Nanoprecipitation
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Engineered nucleocytosolic vehicles for loading of programmable editors.

Julian Geilenkeuser1, Niklas Armbrust1, Emily Steinmaßl1

  • 1Institute for Synthetic Biomedicine, Helmholtz Munich, Neuherberg, Germany; Department of Bioscience, TUM School of Natural Sciences, Technical University of Munich, Munich, Germany.

Cell
|April 10, 2025
PubMed
Summary

We developed a virus-like particle (VLP) delivery system for gene editors, improving therapeutic potential. This novel system enhances gene editing efficiency in various cell types and animal models.

Keywords:
VLPsbase editingcell therapygene deliverygene therapygenome editingin vivo deliveryprime editingvirus-like particles

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Area of Science:

  • Molecular Biology
  • Biotechnology
  • Gene Therapy

Background:

  • Gene editing technologies offer significant therapeutic potential but face challenges in safe and efficient delivery.
  • Developing effective delivery vehicles is crucial for advancing gene editing applications in medicine.

Purpose of the Study:

  • To engineer a novel virus-like particle (VLP) system for enhanced delivery and efficacy of gene editors.
  • To improve the stability and loading of gene editing components within the delivery vehicle.
  • To demonstrate the broad applicability and therapeutic potential of the VLP system.

Main Methods:

  • Development of a VLP system with nucleocytosolic shuttling vehicles for retrieving pre-assembled Cas-effectors.
  • Utilizing aptamer-tagged guide RNAs for preferential loading of editor ribonucleoproteins (RNPs).
  • Incorporating Csy4/Cas6f to protect prime editing guide RNAs (pegRNAs) and engineering minimal packaging/budding modules.

Main Results:

  • The VLP system achieved preferential loading of fully assembled editor RNPs.
  • Enhanced efficacy of prime editing, base editing, trans-activators, and nuclease activity coupled to homology-directed repair was observed across diverse cell types.
  • Superior per-VLP editing efficiency was demonstrated in primary T lymphocytes and mouse models of inherited retinal disease.

Conclusions:

  • The engineered VLP system provides a robust platform for efficient and safe delivery of gene editors.
  • This technology shows significant promise for therapeutic applications, particularly in treating genetic disorders.
  • The modular design allows for bottom-up engineering of enveloped delivery vehicles for various gene editing tools.