SYNTHETIC-POLYMERS FOR VECTORIAL DELIVERY OF DNA - CHARACTERIZATION 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 vect or DNA. Here we have characterised the interaction between DNA and pol ylysine of varying molecular weight average (4, 24, 54, 224 k) using e thidium bromide fluorescence to monitor formation of complexes and the ir disruption by poly(L)aspartic acid (PAA). All poly(L)lysines were a ble to form complexes with DNA, and sizes measured by photon correlati on spectroscopy (PCS) were greater for the larger poly(L)Iysine molecu lar weight fractions (ranging from 37 to 207 nm average diameter). Com plexes based on larger poly(L)lysines showed a sigmoidal destabilisati on by PAA while complexes based on smaller pLLs showed more linear dis ruption. Complexes formed between DNA and a linear A-B poly(ethylene g lycol)-poly(L)lysine showed an average diameter approximately 53 nm de termined 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.