HIV TAT peptide modifies the distribution of DNA nanolipoparticles following convection-enhanced delivery

Mol Ther. 2008 May;16(5):893-900. doi: 10.1038/mt.2008.36. Epub 2008 Mar 11.


We evaluated gene transfer using PEGylated bioresponsive nanolipid particles (NLPs) containing plasmid DNA administered by convection-enhanced delivery (CED) into orthotopically implanted U87-MG tumors in rat brain. We hypothesized that attachment of the human immunodeficiency virus trans-acting transcriptional activator peptide (TATp) to pH-sensitive, reduction-sensitive NLPs would increase gene transfer. TATp was attached either directly to a phospholipid (TATp-lipid) or via a 2-kd polyethylene glycol (PEG) to a lipid (TATp-PEG-lipid). Incorporation of 0.3 mol% TATp-PEG into pH-sensitive NLPs improved transfection 100,000-fold compared to NLPs in culture. In the brain or implanted tumors, the TATp-PEG restricted NLP convection to regions adjacent to the infusion catheter. Gene transfer in the brain from TATp-PEG NLPs, measured by green fluorescent protein (GFP) expression, was substantially greater than from NLPs adjacent to the catheter. Gene transfer using TATp-PEG NLPs, measured by luciferase expression, was 8-12-fold greater than from a 1,2-dioleoyl-3-trimethylammonium-propane/cholesterol cationic lipoplex but 13-27-fold less than from the NLPs. Brain luciferase expression was localized in perivascular macrophages. Thus a cationic ligand, such as the TATp-PEG-lipid, can dramatically increase gene expression in culture, in the normal brain, and in implanted tumors; however, restriction of NLP distribution to the vicinity of the infusion catheter reduces the absolute level of gene transfer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism
  • DNA / metabolism
  • Gene Expression Regulation*
  • Gene Products, tat / genetics*
  • Gene Products, tat / physiology
  • Gene Transfer Techniques*
  • Genetic Therapy / methods
  • HIV / metabolism*
  • Humans
  • Liposomes / chemistry*
  • Nanoparticles / chemistry*
  • Neoplasm Transplantation
  • Peptides / chemistry
  • Plasmids / metabolism
  • Rats


  • Gene Products, tat
  • Liposomes
  • Peptides
  • DNA