γ-Polyglutamic acid-coated vectors for effective and safe gene therapy

摘要

In the present study, we developed some novel gene delivery vectors, coated cationic complexes with γ- polyglutamic acid (γ-PGA) for effective and safe gene therapy. Cationic complexes were constructed with pDNA and cationic vectors, such as poly-L-arginine hydrochloride (PLA), poly-L-lysine hydrobromide (PLL), N-[1-(2, 3-dioleyloxy) propyl]-N, N, N-trimethylammonium chloride (DOTMA)-cholesterol (Chol) liposomes, and DOTMA-dioleylphosphatidylethanolamine (DOPE) liposomes. The cationic complexes showed high gene expression with strong cytotoxicity in melanoma B16-F10 cells. The cationic complexes were also strongly toxic to erythrocytes. On the other hand, the γ-PGA was able to coat all cationic complexes and form stable nano-sized particles with negative charges. These γ-PGA-coated complexes had high gene expression without cytotoxicity and toxicities to the erythrocytes. In in vivo transfection experiments, polyplexes showed high transfection efficiency over 105 RLU/g in the lung tissue after intravenous injection, although γ- PGA-coated polyplexes showed a high value in the spleen. High transfection efficiency in lipoplexes and γ- PGA-coated lipoplexes was observed in the spleen and lung. Thus, γ-PGA-coated vectors are useful for clinical gene therapy.