One-Stop Solution for Anti-Membrane Protein sdAb Development

Creative Biolabs is a leading service provider that focuses on single domain antibody (sdAb) discovery and development. Based on our deep understanding of various membrane proteins, our scientists have built up one-stop solutions to generate high-quality single domain antibodies that can properly recognize the target membrane protein for our customers all over the world.

Membrane Protein - A Class of the Most Important & Challenging Targets for Antibody Development

In most cancer diseases, therapeutic targets are cell surface molecules which are predominantly comprised of membrane proteins. Membrane protein is a class of targets that are composed of a wide range of structurally and functionally diverse proteins involved in a variety of important physiological and homeostatic processes, such as:

• Membrane receptor proteins relay signals between the cell's internal and external environments.
• The molecules and ions across the membrane via transport proteins.
• Membrane proteins may present enzyme activity, such as oxidoreductase and hydrolase.
• Cell adhesion molecules allow cells to identify each other and interact.

In terms of the ability to activate/block the downstream function or promote the analysis of 3D structure, antibodies that can direct against target membrane proteins have played critical roles as either therapeutic/diagnostic agents or research tools. However, membrane protein is also one of the most challenging targets to generate high-quality antibodies, and the limitations usually include: 1) the challenge of designing and producing properly antigen that can mimic the epitopes of naïve membrane proteins; 2) homology issues which may cause immunological tolerance; 3) potential steric issues caused by the multi-pass membrane proteins, in which some epitopes cannot be reached by conventional antibodies.

Developing High-Quality Anti-Membrane Protein sdAb at Creative Biolabs

Fortunately, Creative Biolabs has solutions to overcome all these limitations by using sdAb instead of the full-length IgG or other antibody fragments. sdAb is a unique antibody format that consists of a single monomeric variable domain without CH domain or light chain in conventional Fab region. It is usually generated from camelid or cartilaginous fishes, which indicate relatively low homology for most of the membrane proteins associated with therapeutic targets. Taking advantages of the small size, high stability, and great penetrability, sdAb can carry the task to recognize even the most cryptic epitopes. In the meantime, our scientists have also integrated our Magic™ membrane protein platform and DNA immunization strategy into the profiles, which can offer comprehensive solutions for antigen design and preparation. Therefore, the development of single domain antibodies against membrane proteins is now highly sought after for research, diagnostic, and therapeutic purposes, and our one-stop solution could be the most efficient option to achieve your purpose with high success rate.

Typical Pathway for Membrane Protein-Specific sdAb Development

Phase I Target Identification

	Antigen Design & Preparation Starting with in silico sequence of targets, our scientists can handle the intact design and preparation processes to fit the demands for sdAb discovery. You can also provide the prepared target for further processes.
Target Expression Cell Lines Positive cell lines that express the target of interest can be generated and employed as antigen for sdAb development. The corresponding negative cell lines which do not express the target will be used as a control to ensure reliability. You can also provide these cell lines for further processes.	Epitopes Mimic Peptides Peptides can be designed and synthesized properly to mimic the desired target epitopes. Carrier proteins will be conjugated for short peptides to ensure immunogenicity or promote screening processes.	Target Expression Plasmids For antigens which are difficult to be expressed or purified, the corresponding plasmids can be constructed for DNA immunization, which can permit in vivo antigen production and trigger the desired immune response.
Lipoparticle Lipoparticle is highly purified virus-like particle (VLP) that contains intact, native membrane proteins harvested from host cells. It has a much smaller size, increased stability, and higher display density than target expressing cell lines, which can be used as both antigen and screening target.	Nanodisc Nanodisc is formed by self-assembled phospholipid and membrane scaffold protein. It is a powerful tool to keep membrane protein in a naïve form with the folded conformation and intact function.	Proteoliposome Proteoliposome can well keep membrane proteins correctly folded with their naïve structures, activities, and functions, it has been frequently used to study membrane protein for antibody development, binding tests, and functional assays.

Phase II Discovery

Conventional Immunization This strategy can elicit responses from several easily accessible sites thus contribute to the development of antibodies with high specificity and affinity.	DNA Immunization Starting with in silico sequence of targets, our scientists can handle the intact design and preparation processes to fit the demands for sdAb discovery. You can also provide the prepared target for further processes.	Whole Cell Immunization Starting with in silico sequence of targets, our scientists can handle the intact design and preparation processes to fit the demands for sdAb discovery. You can also provide the prepared target for further processes.
B-Cell Sorting Based sdAb Discovery To bring our customers impeccable service of sdAb discovery, our seasoned scientific team has developed integrated B-cell sorting platform to maximize our customers' success in discovering valuable sdAbs.	Immune Library Based sdAb Discovery Our scientists are confident in generating high-quality immune library and performing comprehensive library screening and validation strategies to select the best-fit sdAbs for your targets.		Premade Library Based sdAb Discovery Creative Biolabs has owned a series of high-quality in-house sdAb libraries (originated from camels, llamas as well as humans) which are great resources available for your sdAb discovery project.

Phase III Characterization

Functional sdAb Screening A series of assays are available to further analysis and screening sdAb candidates with desired functions, including but not limited to binding assays, immunomodulation assessments (activation or blocking), neutralizing assay, Fc profiling (ADCC, ADCP, CDC, etc.), endocytosis & internalization assays, cell proliferation assays.	sdAb Affinity Measurement A series of technologies are available to measure the affinity of specific sdAbs with the most advanced systems (e.g. Biacore, ProteOn, Octet).	sdAb Stability Evaluation A series of custom analytical approaches are available to assess the stability of specific sdAbs upon your request, including the evaluation of aggregation and stability under extreme condition.
De Novo sdAb Sequencing Equipped with our proprietary database assisted shotgun sequencing (DASS) technology, now Creative Biolabs provides the soluble and functional sdAbs sequencing services with 100% coverage and 100% accuracy.	sdAb Paratope Mapping Paratope, also named as an antigen-binding site, is a part of the antibody which allows the recognition and binding to an antigen. Paratope mapping is a powerful technology to understand the antigen-binding site well and plays an important role in vaccines and biotherapeutics discovery.	sdAb Epitope Mapping Epitopes consist of groups of amino acids which interact with antibodies and therefore determine the antigenicity. Now we can provide the epitope mapping services with 100% accuracy and efficiency.
More Creative Biolabs offers a variety of sdAb characterization services for your project. Our scientists can also provide customized solutions to meet your specific demands.

Phase IV Development

Multivalent sdAb Development The development of multivalent sdAb provides various alternative formats which can endow sdAbs with specific properties, such as extended half-life, increased avidity, and the recognition of different targets.	sdAb Affinity Maturation Elaborate procedures can be tailored to develop sdAbs with increased affinity against the target of interest.	sdAb Conjugation A variety of custom sdAb conjugations are available of your choice.
sdAb Humanization Creative Biolabs provides elegant sdAb humanization strategy, which is an efficient approach to reduce or eliminate the immunogenicity of sdAb drug candidates.
More Creative Biolabs offers a variety of sdAb development services for your project. Our scientists can also provide customized solutions to meet your specific demands.

Phase V Manufacture

sdAb Scale-up Production Transient transfection method can be employed for custom sdAb production via either E. coli or mammalian system.

sdAb Stable Cell Line Construction Our scientists are professional in constructing stable cell lines with high yield to meet your demands of long-term sdAb production.

Features of One-Stop Anti-Membrane Protein sdAb Development

• Comprehensive membrane protein preparation and immunization strategies (e.g. lipoparticle, cell line construction, and DNA immunization)
• The scientific group with extensive experience in dealing with membrane protein, who can tailor the most suitable solutions for your projects
• Advanced platforms to ensure the best achievement for every single step (from the membrane protein preparation to the sdAb candidates' validation)
• Multiple pathways to enhance the success rate
• Reliable lab report with timely update
• Affordable price with the best quality

With years of experience, our scientists have developed a variety of sdAbs against membrane proteins. We are always pleased to offer the best service and the most qualified outcomes to meet your specific requirements. If you are interested in developing novel sdAbs against the membrane protein of interest, please do not hesitate to contact us for more details.

Case Study

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sdAb Development for Soluble Protein Target

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sdAb Development for Hapten Target

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sdAb Development for 3 Targets via 1 Camelid Immunization

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sdAb Development via Premade HuSdL-1 Library

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sdAb Development for Low Immunogenic Target

All services are provided for research purposes only. Our services cannot be used for clinical or therapeutic applications.