Recombinant elastin based nanoparticles for targeted gene therapy

Among viruses, lentiviral vectors have been popular vectors for gene delivery due to their efficient mode of gene delivery. However, the non-specific delivery of genes associated with lentiviral vectors may result in undesirable side effects. Here, we propose a heterogeneous nanoparticle delivery system for targeted delivery of lentiviral particles containing a therapeutic gene. The heterogeneous nanoparticles consist of the low density lipoprotein receptor 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 while homogeneous nanoparticles comprising of LDLR3-ELP alone blocked viral transduction, heterogeneous nanoparticles comprising of KGF-ELP and LDLR3-ELP enhanced viral transduction in cells expressing high levels of the KGF receptors compared to cells expressing low levels of KGF receptors. Overall, this novel design may help with the targeting of specific cells that overexpressed growth factor such as KGF receptors.