The rapid growth of the therapeutic protein market calls for more efficient purification methods. Various aggregating tags have recently emerged as simple, fast, cost-effective and column-free technologies for protein (and peptide) purification. In general, these column-free protein purification technologies involve the use of aggregating tags that induce the target protein into insoluble aggregates. These aggregates can be easily separated from soluble impurities and the target protein or peptide is then liberated by a cleavage process. This review summarizes the current state-of-the-art in using aggregating tags for protein purification. The methods are here categorized as follows: (1) tags that allow soluble expression of target protein in vivo and induce aggregation in vitro; (2) tags that induce soluble expression and self-assembling of target protein on insoluble biological polyester beads in vivo; (3) tags that induce formation of inactive aggregates in vivo; (4) tags that induce formation of active aggregates in vivo.
Keywords: Aggregating tags; Cleavable tags; Protein purification; Therapeutic proteins.