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Facile Preparation of Internally Self-assembled Lipid Particles Stabilized by Carbon Nanotubes
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Nanoengineering artificial lipid envelopes around adenovirus by self-assembly.

Ravi Singh1, Khuloud T Al-Jamal, Lara Lacerda

  • 1Nanomedicine Laboratory, Centre for Drug Delivery Research, The School of Pharmacy, University of London, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom.

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Researchers created artificial lipid envelopes for adenoviruses (Ad) without altering the virus. This novel method controls viral properties, enhancing gene transfer in tumor models while improving safety by blocking cellular entry in monolayers.

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Area of Science:

  • Biotechnology
  • Nanotechnology
  • Virology

Background:

  • Adenoviruses (Ad) are widely used viral vectors for gene therapy.
  • Modifying Ad surface chemistry is challenging, often requiring genome alteration or complex conjugation.
  • Developing facile methods to engineer viral properties is crucial for advancing gene therapy applications.

Purpose of the Study:

  • To develop a novel, reproducible, and facile method for creating artificial lipid envelopes around adenoviruses.
  • To investigate how different lipid bilayer compositions influence the physicochemical and biological properties of enveloped adenoviruses.
  • To assess the gene transfer efficiency and cellular interactions of artificially enveloped adenoviruses in various cell culture models.

Main Methods:

  • Self-assembly of lipid molecules around the native viral capsid to form artificial envelopes.
  • Characterization of physicochemical properties (size, aggregation, stability, charge) of enveloped adenoviruses.
  • Evaluation of gene transfer function in monolayer cell cultures and 3D tumor spheroid models, assessing binding, cellular uptake, and gene expression.

Main Results:

  • Artificial envelopes were constructed without altering the adenovirus genome or capsid surface chemistry.
  • Zwitterionic envelopes blocked coxsackie and adenovirus receptor (CAR) binding, while cationic envelopes enhanced cell membrane binding.
  • Envelopment with zwitterionic or cationic lipids ablated gene expression in monolayers by blocking endosomal escape.
  • Lipid envelopes in the fluid phase enhanced vector penetration into tumor spheroids and delayed gene expression compared to non-enveloped Ad.

Conclusions:

  • Artificial lipid envelopes provide a general strategy to engineer non-enveloped viruses at the nanoscale.
  • This method allows rational control over viral biological properties, including gene transfer efficiency and cellular interactions.
  • The approach eliminates production and purification challenges associated with traditional surface-modified viruses, offering a promising avenue for gene therapy development.