Field of Biophysics, Cornell University, Ithaca, NY 14853, USA.
Robert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY 14853, USA.
Adv Drug Deliv Rev. 2023 Feb;193:114618. doi: 10.1016/j.addr.2022.114618. Epub 2022 Nov 11.
Mucins represent a largely untapped class of polymeric building block for biomaterials, therapeutics, and other biotechnology. Because the mucin polymer backbone is genetically encoded, sequence-specific mucins with defined physical and biochemical properties can be fabricated using recombinant technologies. The pendent O-glycans of mucins are increasingly implicated in immunomodulation, suppression of pathogen virulence, and other biochemical activities. Recent advances in engineered cell production systems are enabling the scalable synthesis of recombinant mucins with precisely tuned glycan side chains, offering exciting possibilities to tune the biological functionality of mucin-based products. New metabolic and chemoenzymatic strategies enable further tuning and functionalization of mucin O-glycans, opening new possibilities to expand the chemical diversity and functionality of mucin building blocks. In this review, we discuss these advances, and the opportunities for engineered mucins in biomedical applications ranging from in vitro models to therapeutics.
粘蛋白是一类尚未充分开发的聚合结构单元，在生物材料、治疗药物和其他生物技术领域具有广泛的应用。由于粘蛋白聚合物主链是由基因编码的，因此可以使用重组技术来制备具有特定序列、明确物理化学性质的粘蛋白。粘蛋白的侧链糖基在免疫调节、抑制病原体毒力等生物化学活性中起着越来越重要的作用。最近在工程细胞生产系统方面的进展，使人们能够大规模合成具有精确调控聚糖侧链的重组粘蛋白，为基于粘蛋白的产品的生物功能调节提供了令人兴奋的可能性。新的代谢和化学酶策略使粘蛋白 O-聚糖的进一步调控和功能化成为可能，为扩大粘蛋白构建模块的化学多样性和功能性开辟了新的可能性。在本文中，我们讨论了这些进展，以及在从体外模型到治疗药物等生物医学应用中，工程粘蛋白的应用机会。
