IN-VITRO GENE DELIVERY BY DEGRADED POLYAMIDOAMINE DENDRIMERS

Citation
Mx. Tang et al., IN-VITRO GENE DELIVERY BY DEGRADED POLYAMIDOAMINE DENDRIMERS, Bioconjugate chemistry, 7(6), 1996, pp. 703-714
Citations number
22
Categorie Soggetti
Biology,Chemistry,"Biochemical Research Methods
Journal title
ISSN journal
10431802
Volume
7
Issue
6
Year of publication
1996
Pages
703 - 714
Database
ISI
SICI code
1043-1802(1996)7:6<703:IGDBDP>2.0.ZU;2-9
Abstract
Transfection of cultured cells has been reported using complexes betwe en DNA and spherical cationic polyamidoamine polymers (Starburst dendr imers) that consist of primary amines on the surface and tertiary amin es in the interior. The transfection activity of the dendrimers is dra matically enhanced (> 50-fold) by heat treatment in a variety of solvo lytic solvents, e.g., water or butanol. Such treatment induces signifi cant degradation of the dendrimer at the amide linkage, resulting in a heterodisperse population of compounds with molecular weights ranging from the very low (<1500 Da) to several tens of kilodaltons. The comp ound facilitating transfection is the high molecular weight component of the degraded product and is denoted as a ''fractured'' dendrimer. T ransfection activity is related both to the initial size of the dendri mer and its degree of degradation. Fractured dendrimers exhibit an inc reased apparent volume change as measured by an increase in the reduce d viscosity upon protonation of the terminal amines as pH is reduced f rom 10.5 to 7.2 whereas intact dendrimers do not. Dendrimers with defe ctive branching have been synthesized and also have improved transfect ion activity compared to that of the intact dendrimers. For a series o f heat-treated dendrimers we observe a correlation between transfectio n activity and the degree of flexibility, computed with a random cleav age simulation of the degradation process. We suggest that the increas ed transfection after the heating process is principally due to the in crease in flexibility that enables the fractured dendrimer to be compa ct when complexed with DNA and swell when released from DNA.