Bioengineered heparin: Advances in production technology

Heparin, a highly sulfated glycosaminoglycan, is considered an indispensable anticoagulant with diverse therapeutic applications and has been a mainstay in medical practice for nearly a century. Its potential extends beyond anticoagulation, showing promise in treating inflammation, cancer, and infectious diseases such as COVID-19. However, its current sourcing from animal tissues poses challenges due to variable structures and adulterations, impacting treatment efficacy and safety. Recent advancements in metabolic engineering and synthetic biology offer alternatives through bioengineered heparin production, albeit with challenges such as controlling molecular weight and sulfonation patterns. This review offers comprehensive insight into recent advancements, encompassing: (i) the metabolic engineering strategies in prokaryotic systems for heparin production; (ii) strides made in the development of bioengineered heparin; and (iii) groundbreaking approaches driving production enhancements in eukaryotic systems. Additionally, it explores the potential of recombinant Chinese hamster ovary cells in heparin synthesis, discussing recent progress, challenges, and future prospects, thereby opening up new avenues in biomedical research.