Genospheres: self-assembling nucleic acid-lipid nanoparticles suitable for targeted gene delivery

Gene Ther. 2006 Apr;13(7):646-51. doi: 10.1038/


We describe the assembly of a cationic lipid-nucleic acid nanoparticle from a liquid monophase containing water and a water miscible organic solvent where both lipid and DNA components are separately soluble prior to their combination. Upon removal of the organic solvent, stable and homogenously sized (70-100 nm) lipid-nucleic acid nanoparticles (Genospheres) were formed. The low accessibility (<15%) of the nanoparticle-encapsulated DNA to a DNA intercalating dye indicated well-protected nucleic acids and high DNA incorporation efficiencies. It was demonstrated that Genospheres could be stably stored under a variety of conditions including a lyophilized state where no appreciable increase in particle size or DNA accessibility was observed following reconstitution. Finally, Genospheres were made target-specific by insertion of an antibody-lipopolymer (anti-HER2 scFv (F5)-PEG-DSPE) conjugate into the particle. The target specificity (>100-fold) in HER2 overexpressing SK-BR-3 breast cancer cells was dependent on the degree of PEGylation, where the incorporation of high amounts of PEG-lipid on the particle surface (up to 5 mol%) had only a minor effect on the transfection activity of the targeted Genospheres. In summary, this work describes a novel, readily scalable method for preparing highly stable immunotargeted nucleic acid delivery vehicles capable of achieving a high degree of specific transfection activity.

MeSH terms

  • DNA / administration & dosage*
  • Drug Carriers
  • Gene Targeting
  • Genetic Therapy / instrumentation
  • Genetic Therapy / methods*
  • Humans
  • Immunoglobulin Variable Region / genetics*
  • Liposomes
  • Microscopy, Electron
  • Nanostructures
  • Nanotechnology / methods*
  • Phosphatidylethanolamines
  • Polyethylene Glycols
  • Receptor, ErbB-2 / immunology*


  • Drug Carriers
  • Immunoglobulin Variable Region
  • Liposomes
  • Phosphatidylethanolamines
  • polyethylene glycol-distearoylphosphatidylethanolamine
  • Polyethylene Glycols
  • DNA
  • Receptor, ErbB-2