Novel gene transfer vectors based on artificial recombinant multi-functional oligopeptides

Int J Pharm. 2012 Oct 15;436(1-2):555-63. doi: 10.1016/j.ijpharm.2012.07.001. Epub 2012 Jul 13.

Abstract

Viral vectors, except for their safety concern, have shown high efficiency in both delivery and expression of gene. Here, a series of new gene carriers, comprised of short peptide subunits with special functions to imitate viral vectors, were designed and three vectors, (C(18))(2)KH(4)R(8)GDS, AcKH(4)R(8)GDS and (C(18))(2)KH(4)R(8), designated as ARM1, ARM2, ARM3, respectively, were synthesized and evaluated. The transfection efficiency in vitro was studied in terms of 293T, HepG2 and HeLa cell lines. It was found that the transfection efficiency was enhanced significantly for the vectors (ARM1 and ARM3) with double hydrophobic aliphatic tails. Interestingly, the conjugation of RGDS sequence in vectors displayed no obvious difference in cell adhesion for all of the three cell lines. Moreover, confocal laser scanning microscope results indicated that the peptide/pDNA complexes can enter the cell and nuclei successfully. On the other hand, all the vectors displayed low cytotoxicity. The artificial recombinant multi-block oligopeptides (ARMs) demonstrated here might give a promising potential of the peptide-based vectors in gene therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Survival / drug effects
  • DNA / administration & dosage*
  • DNA / chemistry
  • Genetic Vectors
  • HEK293 Cells
  • HeLa Cells
  • Hep G2 Cells
  • Humans
  • Oligopeptides / administration & dosage*
  • Oligopeptides / chemistry
  • Particle Size
  • Protein Binding
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / chemistry
  • Stearic Acids / chemistry
  • Transfection / methods

Substances

  • Oligopeptides
  • Recombinant Proteins
  • Stearic Acids
  • stearic acid
  • DNA