Synthetic polymers for vectorial delivery of DNA: characterisation of polymer-DNA complexes by photon correlation spectroscopy and stability to nuclease degradation and disruption by polyanions in vitro

Synthetic polymers or multifunctional block copolymers can be used as gene delivery vectors, designed for self assembly with expression vector DNA. Here we have characterised the interaction between DNA and polylysine of varying molecular weight average (4, 24, 54, 224 k) using ethidium bromide fluorescence to monitor formation of complexes and their disruption by poly(L)aspartic acid (PAA). All poly(L)lysines were able to form complexes with DNA, and sizes measured by photon correlation spectroscopy (PCS) were greater for the larger poly(L)Iysine molecular weight fractions (ranging from 37 to 207 nm average diameter). Complexes based on larger poly(L)lysines showed a sigmoidal destabilisation by PAA while complexes based on smaller pLLs showed more linear disruption. Complexes formed between DNA and a linear A-B poly(ethylene glycol)-poly(L)lysine showed an average diameter approximately 53 nm determined by PCS. The block copolymer did not improve the stability of complexes to destabilisation by PAA but did increase resistance of the complexes to nucleolytic degradation. (C) 1997 Elsevier Science B.V.