Gene Transfer Using StarburstTM Dendrimers

Abstract : The new class of synthetic, highly branched, spherical Starburst(Trademark) polyamidoamine (PAMAM) dendrimer polymers is unique in structure. These molecules are uniform in size with a high density of charged primary amino groups restricted to the surface, as well as being highly soluble and stable in aqueous solution. The major structural differences in PAMAM dendrimers relate to the initiator molecule, either ammonia (NH3) as trivalent or ethylenediamine (EDA) as a tetravalent core, that starts the stepwise polymerization process and determines the overall shape, density, and surface charge of the molecule. With each new layer, or generation, the molecular weight of the polymer more than doubles and the number of surface amino groups exactly doubles. Dendrimers range in size from 10 to 130 A, with each polymerization step adding approximately 10 A to the diameter of the molecule. At least 10 generations of both types of PAMAM dendrimers (NH3 and EDA core) can be synthesized (Tomalia et al., 1990). Each final dendrimer preparation is purified using ultrafiltration and structurally characterized using a number of techniques including electrospray-ionization mass spectroscopy, C-13 and H-1 nuclear magnetic resonance spectroscopy, size exclusion chromatography, capillary electrophoresis, high performance liquid chromatography (HPLC), and gel electrophoresis (Tomalia et al, 1990). Starburst(Trademark) PAMAM dendrimers are identified using a standard nomenclature; for example G10 EDA is the 10th generation of an EDA core dendrimer. PAMAM dendrimers are currently the only class of dendritic macromolecules that are reliably produced in large quantities and that can be precisely synthesized over a broad range of molecular weights.