Center for Biotechnology & Interdisciplinary Studies, Department of Chemical & Biological Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
Trends Biotechnol. 2013 Nov;31(11):612-20. doi: 10.1016/j.tibtech.2013.07.002. Epub 2013 Aug 7.
Monoclonal antibodies are attractive therapeutics for treating a wide range of human disorders due to their exquisite binding specificity and high binding affinity. However, a limitation of antibodies is their highly variable and difficult-to-predict propensities to aggregate when concentrated during purification and delivery. Despite the large size and complex structure of antibodies, recent findings suggest that antibody solubility can be dramatically improved using rational design methods in addition to conventional selection methods. Here, we review key advances and unmet challenges in engineering the variable and constant regions of antibody fragments and full-length antibodies to resist aggregation without reducing their binding affinity. These experimental and computational discoveries should accelerate the development of robust algorithms for designing aggregation-resistant antibodies.
单克隆抗体由于其高度特异性的结合和高亲和力，成为治疗多种人类疾病的有吸引力的治疗方法。然而，抗体的一个局限性是，在纯化和输送过程中浓缩时，它们具有高度可变和难以预测的聚集倾向。尽管抗体的体积庞大且结构复杂，但最近的研究结果表明，除了传统的选择方法外，还可以使用合理的设计方法极大地提高抗体的溶解度。在这里，我们回顾了在不降低结合亲和力的情况下，设计抗体片段和全长抗体的可变区和恒定区以抵抗聚集的关键进展和未满足的挑战。这些实验和计算发现应该加速设计抗聚集抗体的稳健算法的发展。
