A combined strategy improves the solubility of aggregation-prone single-chain variable fragment antibodies

► The scFvs show soluble when they are fused with NusA or MBP. ► The scFvs aggregate when cleaving their solubility-enhancing tags. ► The oxidizing bacterial cytoplasm benefits the reduction of aggregation. ► l-Arginine or Tween20 is able to protect the scFvs from aggregation. ► Application of small affinity tags helps obtaining scFvs with high purity.