Abstract: A method for removal of host cell DNA from a sample containing a species of desired protein, virus, or extracellular vesicle comprising the steps of: Loading a substrate bearing an anionic metal affinity ligand with a metal ion, Equilibrating the substrate with a buffer having a pH in the range of pH 6 to pH 10, and a salt concentration in a concentration range up to 1 M which salt is not forming a chemical complex with the anionic metal affinity ligand, Contacting the sample with the metal-loaded anionic metal affinity substrate, Separating the substrate from the sample, wherein the sample has reduced content of contaminating DNA.

Abstract: A method for separating full Adeno-associated virus (AAV) capsids from empty AAV capsids in a buffered mixture comprising full AAV capsids, empty AAV capsids, comprising the steps of contacting the buffered mixture with a first substrate bearing a metal affinity ligand attached to the first substrate, said metal affinity ligand having the ability to complex metal ions via three or more nitrogen atoms, separating empty AAV capsids from full AAV capsids by eluting with a pH gradient, a salt gradient, a metal ion gradient or a combination thereof in the presence of multivalent cations bound to the metal affinity ligand to obtain a purified full AAV capsid fraction.