Novel gene transfer vectors based on artificial recombinant multi-functional oligopeptides.
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.
Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University, Wuhan 430072, PR China.
Kai
K
Han
Juan
J
Yang
Si
S
Chen
Jing-Xiao
JX
Chen
Chen-Wei
CW
Liu
Cao
C
Li
Han
H
Cheng
Ren-Xi
RX
Zhuo
Xian-Zheng
XZ
Zhang
D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry; D005822:Genetic Vectors; D057809:HEK293 Cells; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D009842:Oligopeptides / Q000008:administration & dosage* / Q000737:chemistry; D010316:Particle Size; D011485:Protein Binding; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000737:chemistry; D013229:Stearic Acids / Q000737:chemistry; D014162:Transfection / Q000379:methods
D009842:Oligopeptides; D011994:Recombinant Proteins; D013229:Stearic Acids; C031183:stearic acid; D004247:DNA