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Tissue-specific gene delivery via nanoparticle coating.

Todd J Harris1, Jordan J Green, Peter W Fung

  • 1Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139, USA.

Biomaterials
|October 24, 2009
PubMed
Summary
This summary is machine-generated.

Polymeric gene delivery nanoparticles can be coated with peptides to improve safety and target specific organs. Varying peptide coating density directs gene delivery to the liver or spleen and bone marrow.

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Area of Science:

  • Biomaterials Science
  • Nanotechnology
  • Gene Therapy

Background:

  • Viral gene delivery poses safety concerns.
  • Polymeric gene delivery methods have low in vivo efficacy.
  • Nanoparticle composition is often coupled, limiting functional control.

Purpose of the Study:

  • To develop peptide coatings for gene delivery nanoparticles.
  • To investigate the effect of coatings on nanoparticle properties and tissue-specificity.
  • To improve the safety and efficacy of non-viral gene delivery.

Main Methods:

  • Electrostatically adsorbed poly(glutamic acid)-based peptide coatings were applied to core gene delivery particles.
  • Nanoparticle size and serum interactions were analyzed.
  • Tissue-specificity of gene delivery was assessed in vivo following systemic injection.

Main Results:

  • All peptide coatings reduced toxicity compared to uncoated nanoparticles.
  • Low peptide:DNA ratio (2.5:1 w/w) resulted in large nanoparticles (2 μm) that targeted the liver.
  • High peptide:DNA ratio (20:1 w/w) resulted in small nanoparticles (200 nm) that targeted the spleen and bone marrow.

Conclusions:

  • Peptide coating density is a critical factor in controlling nanoparticle size and serum interaction.
  • Nanoparticle peptide coatings can be engineered to achieve specific tissue targeting for gene delivery.
  • This approach offers a promising strategy for safer and more effective non-viral gene therapy.