Poly-L-glutamic acid derivatives as vectors for gene therapy

This paper describes the synthesis and evaluation of biodegradable derivati ves of poly-L-glutamic acid as suitable vectors for gene therapy. When mixe d with DNA the new polymers self assemble and form polyelectrolyte complexe s. The formation of the complexes and determination of their stability towa rds disruption by serum albumin was monitored by Ethidium bromide (EtBr) fl uorescence spectroscopy. All polymers were able to form complexes and their size, determined by photon correlation spectroscopy, was between 84.5 +/- 2 nm and 96.7 +/- 1.6 nm, depending on the type of polymer and the charge r atio. All complexes were stable towards serum albumin. The results from the biodegradability tests, using tritosomes, show that the polymers are biode gradable and the rate of degradation is influenced by the number of charged groups in the side chains. Haemolysis and red blood cell (RBC) agglutinati on were assessed and compared to poly(L-lysine) (pLL) and polyethyleneimine (pEI). RBC agglutination was monitored with optical microscopy. Results sh ow that the new polymers are less toxic than pLL and pEI. Preliminary trans fection studies show that the polymers are suitable vectors for gene delive ry. (C) 2000 Published by Elsevier Science B.V. All rights reserved.