Recombinant elastin-based nanoparticles for targeted gene therapy

Gene Ther. 2017 Oct;24(10):610-620. doi: 10.1038/gt.2017.54. Epub 2017 Sep 14.

Abstract

Among viruses, lentiviral vectors have been popular vectors for gene delivery due to their efficient mode of gene delivery. However, the nonspecific delivery of genes associated with lentiviral vectors may result in undesirable side effects. Here we propose a heterogeneous nanoparticle (NP) delivery system for targeted delivery of lentiviral particles containing a therapeutic gene. The heterogeneous NPs consist of the low-density lipoprotein receptor repeat 3 (LDLR3) and the keratinocyte growth factor (KGF), each fused to elastin-like polypeptides (ELPs), LDLR3-ELP and KGF-ELP, respectively. Our results show that although homogeneous NPs comprising of LDLR3-ELP alone blocked viral transduction, heterogeneous NPs comprising of KGF-ELP and LDLR3-ELP enhanced viral transduction in cells expressing high levels of the KGF receptors compared with cells expressing low levels of KGF receptors. Overall, this novel design may help with the targeting of specific cells that overexpress growth factor receptors such as KGF receptors.

Publication types

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

MeSH terms

  • Cell Line, Tumor
  • Elastin / genetics*
  • Elastin / metabolism
  • Fibroblast Growth Factor 7 / genetics
  • Fibroblast Growth Factor 7 / metabolism
  • Gene Transfer Techniques*
  • Genetic Therapy / methods*
  • Genetic Vectors / genetics
  • HEK293 Cells
  • Humans
  • Lentivirus / genetics
  • Nanoparticles / metabolism*
  • Receptors, LDL / genetics
  • Receptors, LDL / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism

Substances

  • Receptors, LDL
  • Recombinant Proteins
  • Fibroblast Growth Factor 7
  • Elastin