Fig. 3

Current research tools and models for glycobiology studies. Cancer cell models have been extensively explored as primary research tools. Advances in gene editing technologies have enabled the precise and stable modulation of glycan biosynthesis pathways in mammalian cells, allowing the interrogation of glycosylation functional impact and the production of therapeutic glycoproteins. Cell factory technologies have been used for glycovaccines production, surpassing glycoproteins scalability challenges. The focus is now on progressing beyond 2D genetic glycoengineering towards 3D organotypic models, including high-throughput 3D spheroid cultures employing cell lines without or without genetic manipulation. Notwithstanding, the costly and time-consuming nature of these models remain major challenges. The introduction of computationally supported methods for glycoengineering constitutes the next logical cornerstone to address these limitations. Several transgenic mouse models reflecting the systemic impact of glycan deficiencies have also been developed and extensively employed as pre-clinical tools. Humanized models as patient-derived cancer xenografts (PDX) may add additional translational value. However, the loss of the immune system component poses as a major limitation. Alternatively, the adoption of syngeneic animal models developed from allografted glycoengineered cell lines, which can retain intact immune systems and provide the necessary means to address impact of glycosylation, could pose a valuable tool