In recent years, single domain antibodies (sdAbs) have emerged as groundbreaking tools in antibody therapeutics. With their unique structural properties and superior functionality, these single-domain antibody fragments demonstrate exceptional potential in a wide range of applications. Creative Biogene offers comprehensive single domain antibody services, including library construction, screening, and production, to streamline your research and accelerate development toward clinical applications.

What are dsAbs?

dsAbs, first discovered by Hamers-Casterman and colleagues in 1993, are derived from the heavy-chain-only antibodies (HCAbs) found in camelid serum. Unlike conventional antibodies, these HCAbs naturally lack light chains, and their variable regions, termed VHH or dsAbs, represent the smallest functional antigen-binding domain. Weighing only 15 kDa, dsAbs are about 10% the size of traditional antibodies.

Core Structure and Versatility of dsAbs

The core structure of VHH comprises four conserved framework regions (FRs) and three complementarity-determining regions (CDRs), with the elongated CDR3 crucial for recognizing even cryptic epitopes. Additionally, shark-derived heavy-chain antibodies (IgNAR) have variable domains called VNARs, which are even smaller (~12 kDa) and ideal for specialized applications such as ultrastructural studies.

dsAbs can be customized through genetic engineering to serve diverse applications:

• Clinical Applications

dsAbs have made remarkable advances in treating diseases such as:

• Autoimmune Disorders: Caplacizumab, the first therapeutic single domain antibody, was approved for acquired thrombotic thrombocytopenic purpura (aTTP). Ozoralizumab has been authorized for rheumatoid arthritis.
• Cancer Therapy: dsAbs targeting tumor antigens like HER2 show significant therapeutic effects.
• Neurodegenerative Diseases: With their ability to cross the blood-brain barrier, dsAbs are being explored for Alzheimer's and Parkinson's disease treatments.
• Infectious Diseases: dsAbs neutralizing viral epitopes have demonstrated efficacy against COVID-19 and other pathogens.
• Diagnostics and Imaging: Coupled with radiolabels or fluorescent probes, dsAbs enable precise tumor imaging and early disease diagnosis.

Comprehensive dsAbs Development and Production Services

Creative Biogene is your trusted partner for reliable, innovative, and efficient single domain antibody solutions. Creative Biogene offers comprehensive single domain antibody development services, including alpaca immunization, phage library construction, screening, expression, and validation. We provide three types of single domain antibody libraries: natural (from camel PBLs), immunized (from camels or transgenic mice), and synthetic (using optimized scaffolds and CDR3 randomization), tailored to different project needs.

Additionally, with our extensive expertise in protein engineering and innovative conjugation technologies, we ensure consistency and stability across all production batches. Supported by our experienced technical team and comprehensive documentation system, we strictly adhere to FDA cGMP guidelines and ICH quality standards, delivering reliable and efficient solutions for your research and industrial applications.

• Core Service Overview

1. Efficient Antibody Library Construction

We provide three main types of single domain antibody libraries to meet diverse needs:

• Natural Single Domain Antibody Library: Constructed from peripheral blood lymphocytes (PBLs) of camels, suitable for antigens that are hard to immunize. It offers wide diversity and a high proportion of functional sequences.
• Immunized Library: Generated from immunized camels or transgenic mice, producing high-affinity-specific antibodies against challenging targets. (We recommend using camels, alpacas, and other animals for immunization based on project needs.)
• Synthetic Library: No biological material extraction is required, utilizing optimized scaffolds (e.g., cAbBCII10) with CDR3 randomization and humanization. Ideal for rare or complex antigens.

Quality Assurance:

• High-Quality RNA Extraction and cDNA Synthesis
• Dual PCR Amplification
• High-Capacity Phage Display Libraries

2. High-throughput Antibody Screening

• Phage Display Technology: Multi-round panning to enrich high-affinity candidate molecules, ensuring efficient screening of target antigens.
• Diverse Screening Strategies: Combining biotinylated antigens, cell surface display, and solution-based competition assays to select high-specificity antibodies.

3. Expression Services

Creative Biogene's production platform supports efficient single domain antibody and antibody expression, with capabilities ranging from small-scale to large-scale production, meeting full-process requirements from research to industrialization. We utilize techniques such as affinity chromatography and ion exchange chromatography to ensure product purity exceeds 95%.

4. Stability and Functional Validation

• Physicochemical Stability Testing: We evaluate antibody stability under conditions such as high temperatures, extreme pH levels, and protease degradation.
• Functional Assessments: Including ELISA binding assays, flow cytometry, and cellular functional analyses to comprehensively validate antibody performance.

• Specialized Services

dsAbs also have some limitations, including the need for modification to enhance therapeutic and diagnostic capabilities, reduced serum persistence due to their small size, and the lack of an Fc region to mediate effector functions. Additionally, the production is often camel-derived, raising concerns about potential immune responses in humans.

• Half-Life Extension: By PEGylating and genetically modifying dsAbs, we enhance their in vivo stability.
• Multivalent Single Domain Antibody Design: Genetic modifications to improve binding affinity.
• Humanization: Reduces immunogenicity through framework engineering.
• Conjugation Services: Precise conjugation of dsAbs with drugs or tracers for imaging and therapeutic applications.
• Real-Time Detection Development: Custom portable biosensors providing innovative detection solutions.
• Protein Analysis: Offering protein crystallography and targeted degradation analysis to support antibody mechanism studies.

• Service Timeline

The service timeline is adjusted according to the complexity of the project and customization requirements:

• Service Highlights

1. Comprehensive Technical Support: Creative Biogene's experienced team provides technical guidance throughout the entire process, from demand analysis to final product delivery.
2. Flexible Customization: Library types, screening strategies, and expression systems can be tailored to meet specific client needs.
3. High-Quality Antibody Delivery: We ensure high-affinity, stable antibodies for reliable performance in subsequent research.
4. Rapid Response and Progress Tracking: We provide real-time updates on project progress to ensure efficient project completion.

Contact Us

Creative Biogene is committed to providing high-quality single domain antibody preparation services and supporting scientific breakthroughs. For more information, please feel free to contact us at any time!