Glycosylation profoundly shapes the function and fate of biomolecules, yet its structural complexity demands precise engineering strategies. At Creative Biolabs, our glycosylation engineering platform integrates cutting-edge biochemical and cell-based technologies to customize glycan structures across diverse biomolecule types. We provide targeted solutions including protein/peptide glycoform engineering, Fc glycan optimization in antibodies, and glycolipid synthesis for membrane-based applications. Our services further extend to glycosylated oligonucleotides, small molecule glycodrug development, and polymer modification, enabling functional enhancement and targeted delivery. From design to delivery, we bring the tools and experience to support your innovation, enabling researchers to control glycosylation with unmatched precision.
Fig.1 N-linked and O-linked glycosylation engineering for different therapeutic uses.
Mapping Glycosylation Variants: From Core Structures to Specialized Modifications
Core Glycosylation: N-linked & O-linked Glycosylation
The glycosylation process begins with the transfer of core oligosaccharides onto proteins. In N-linked glycosylation, this occurs co-translationally at Asn-X-Ser/Thr motifs, while O-linked glycosylation initiates post-translationally at serine or threonine residues. These early events shape protein folding, stability, and trafficking. Creative Biolabs offers tailored strategies to control these primary modifications in both prokaryotic and eukaryotic systems.
High Mannose vs. Complex Glycosylation
High mannose glycosylation is characterized by rich mannose branching and is common in early secretory pathways. These structures are recognized by lectins such as mannose receptors, which mediate glycoprotein trafficking and immune clearance. In contrast, complex glycosylation arises through sequential processing in the Golgi, introducing GlcNAc, galactose, sialic acid, and fucose residues. These structures are essential for cell signaling, receptor binding, and pharmacokinetics of therapeutic glycoproteins. We help clients direct their glycoforms toward high mannose or complex profiles, optimizing properties for intended applications in therapeutic protein production or vaccine design.
Specialized Modifications
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Mannose 6-Phosphate (M6P) Glycosylation
: Essential for targeting lysosomal enzymes; deficiencies in M6P tagging are linked to lysosomal storage disorders.
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Sialylation
: The terminal addition of sialic acid prolongs serum half-life and masks recognition by immune receptors, reducing clearance and immunogenicity. For applications requiring fine-tuning of sialic acid content, Creative Biolabs offers cell glycoengineering by manipulating sialylation service, enabling targeted control of sialylation levels in cell lines or glycoproteins.
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Fucosylation
: A single fucose residue at the glycan core (especially in IgG Fc) can suppress or enhance effector functions such as ADCC. Removing core fucose significantly enhances therapeutic antibody potency. Our cell glycoengineering by manipulating fucosylation service allows researchers to modulate core and terminal fucosylation with high precision to optimize immune responses.
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Glycan Branching
: The degree of N-glycan branching affects cell signaling, growth factor response, and immune modulation. We provide cell glycoengineering by manipulating branching service to control glycan complexity and structure across experimental or production cell lines.
These nuanced modifications can be selectively introduced using our advanced glycoengineering platforms to meet specific goals in drug design.
Creative Biolabs: Tailored Glycosylation Solutions
At Creative Biolabs, we support biologics developers with a full spectrum of precision glycoengineering services, enabling custom modification of proteins, antibodies, oligonucleotides, lipids, small molecules, and polymers. Each service is developed to address the distinct requirements of glycosylation across biomolecule classes.
We offer end-to-end solutions for engineering glycoproteins with defined glycoforms. Whether you need uniform high mannose for vaccine candidates or complex-type glycans for receptor targeting, we design and express tailored glycoproteins using:
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Host cell line glycosylation engineering
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In vitro glycan remodeling using purified enzymes
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Chemoenzymatic remodeling protocols
Our workflow supports vaccine antigens, cytokines, growth factors, and structural glycoprotein studies.
Antibody efficacy is intrinsically tied to Fc glycosylation. We provide complete glycan remodeling services to modulate immune effector functions:
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Defucosylation for enhanced ADCC in oncology applications
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Controlled sialylation for anti-inflammatory properties
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Custom hybrid or complex glycoforms for pharmacokinetics tuning
Our platform allows batch-specific Fc glycoform design, especially for monoclonal, bispecific, and Fc-fusion constructs.
Glycolipids are key mediators of membrane dynamics, immune recognition, and pathogen-host interactions. We design and synthesize glycolipids with defined glycan headgroups for use in:
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Vaccine antigen design (e.g., gangliosides, globosides)
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Liposome targeting
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Host-pathogen interaction assays
We offer chemical synthesis, glycosyltransferase-mediated assembly, and analytical profiling of custom glycolipids.
Creative Biolabs offers site-specific glycosylation of oligonucleotides to enhance delivery, stability, and tissue targeting for RNA-based therapeutics. We provide:
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Mannose-modified oligonucleotides for dendritic cell targeting
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GalNAc-siRNAs/ASOs for efficient liver uptake via ASGPR
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Sialylated oligonucleotides for prolonged circulation time
We support siRNAs, antisense oligonucleotides, aptamers, and mRNA modifications.
We use glycosylation to improve drug solubility, targeting, and clearance profiles:
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Oncology drugs (e.g., glycosylated anthracyclines)
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CNS compounds (e.g., sugar-masked neuropeptides)
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Anti-infectives with tissue-specific uptake
Our chemoenzymatic and synthetic platforms enable glycoside introduction at specific molecular positions. We provide custom design, synthesis, and characterization for drug candidates in oncology, infectious diseases, and CNS applications.
Creative Biolabs designs glycopolymer platforms with customizable glycan displays to support drug delivery, regenerative medicine, and biosensor development. We specialize in PEG, PLGA, and polysaccharide modifications with terminal mannose, sialic acid, or fucose residues.
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Glycan-sensitive linkers for triggered drug release
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Adhesive scaffolds with sialic acid, fucose, or mannose for targeted cell interaction
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Glycosylated coatings to minimize nonspecific binding on devices
Why Choose Creative Biolabs?
With a robust understanding of glycoprotein glycosylation across all its forms—high mannose, complex, fucosylation, sialylation, and more—Creative Biolabs provides:
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Advanced glycan engineering tools
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Fully customizable workflows
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High-yield, site-specific modifications
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End-to-end project support from design to validation
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Uncompromising data quality and reproducibility
Each project demands a specific glycan profile. Whether you're enhancing ADCC in antibodies, extending the half-life of therapeutic proteins, or improving siRNA uptake via glycan-mediated targeting, Creative Biolabs delivers reliable, scalable, and scientifically tailored glycosylation solutions. Ready to build your ideal glycoform? Contact our scientists to discuss your project tailored to your goals!
Reference
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Zhong, Xiaotian, et al. "New opportunities in glycan engineering for therapeutic proteins." Antibodies 11.1 (2022): 5. Distributed under Open Access license CC BY 4.0, without modification. https://doi.org/10.3390/antib11010005
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