The single domain antibody (sdAb) from camelid, also known as V_HH, plays an important role in the antibody research of cancer, HIV, and other diseases. With years of study, Creative Biolabs has developed a series of Premade Single Domain Antibody Library that enables rapid discovery of large numbers of high-potency single domain antibodies against the interest targets. Based on our well-established platform, we provide unique single domain antibody library screening service for our customers all over the world.

Single Domain Antibody Library

sdAbs are under a rapid development and becoming increasingly popular in various applications. Due to its small size and high stability, sdAbs enable to access "hidden" epitopes which the full-length antibody or other antibody fragments are unable to recognize. Meanwhile, they can penetrate into difficultly accessible tissues, as well as cross the blood-brain-barrier without the assist of any transporters. In addition, sdAbs comprise greater affinity and selectivity, therefore, promising lower side effects and better efficacy.

Currently, display technology based library construction and screening methods are the most popular and reliable ways to discover novel single domain antibodies. Creative Biolabs has extensive experience in phage display realm and can offer premade single domain antibody library to meet our client's demands of sdAb discovery. Our premade single domain antibody library was constructed based on either camelized human VH3 in FR2 or naïve camelid V_HH repertoire. These premade sdAb libraries are ready-to-use, which can save our clients' valuable time and budget from animal immunization and library construction. With the provided target, our scientist can simply begin with the library screening and provide the specific sdAbs in around 3 months. Meanwhile, we are the expert to offer immune sdAb library construction service as well.

Screening Approaches

Fig.1 Premade Antibody Library Construction and Screening
(Hoogenboom, 2005).

With more than ten years' specific experience in phage display technology, our scientists are confident in offering the best and most comprehensive library screening services towards a broad spectrum of targets, especially based on our premade sdAb libraries.

We can tailor custom antigen production service for our clients to prepare the interest targets for further screening. We also accept targets that provided by our clients, which including but not limited to:

• Whole Cells/Tissues
• Peptides/Haptens
• Recombinant Proteins
• Membrane Proteins
• Other in vivo Targets

Meanwhile, in order to meet our customers' specific requirements and their various research objectives, our scientists are pleased to perform phage display library screening via multiple strategies:

• Solid-Phase Screening
• Solution-Sorting Screening
• Cell-based Screening
• In vivo Screening
• Ex vivo Screening

In addition, we can also license these premade sdAb libraries to our clients who prefer to screen the novel sdAbs themselves. Deliverable of the licensed library will include the library, a detailed user manual, host strain, primer used for sequencing, and other materials that can help our clients achieve their goals of selecting unique sdAbs.

Premade SdAb Library Screening Services

In terms of our unparalleled premade libraries and advanced phage display technology platform, Creative Biolabs is pleased to offer the most comprehensive premade library screening services to meet every client's requirement, as well as contribute greatly to the success of your research goals. Besides the sdAb libraries, we also provide such screening services based on other kinds of premade antibody libraries and peptide libraries that can fit your various demands. If you are interested in such premade library screening services or plan to license our libraries, please feel free to inquiry us for more details.

Published Data

• The Isolation of Neutralizing SdAbs from a Synthetic SdAb Library

Fig. 2 VHH library generation pipeline. (Dmitri Dormeshkin, 2022)

COVID-19 not only caused the global crisis, but also accelerated the development of vaccines and the discovery of antibodies. In this article, scientists reported a process for the development of a synthetic source VHH library for separating the binding domain of VHH binders from SARS-CoV-2-related variants. Among the 10¹¹ different phage display libraries synthesized, they identified many nanomole range affinity VHH conjugates by screening a novel synthetic humanized antibody library. In order to explore the method of affinity improvement, the researchers matured the affinity by CDR1 and CDR2 shuffling, and two kinds of conjugates were developed by constructing the multivalent trimer VHH fusion protein. These constructs are weakly affected by most SARS-CoV-2 mutations, and they retain a moderate binding to BA.4\5.

• CDH17 SdAbs Screening

Fig. 3 Binding specificity of E8 sdAb to CDH17 in CDH17-overexpressing and -knockdown cell lines respectively. (Jingbo Ma, 2022)

Cadherin 17 (CDH17) is a membrane protein highly expressed in digestive system cancer. In this paper, the researchers screened CDH17 domains 1–3 from the initial single-domain antibody phage library and successfully obtained two high-affinity and high-specificity anti-human CDH17 single-domain antibodies (A1 and E8). These sdAbs can specifically bind to CDH17 protein and CDH17 positive gastric cancer cells. E8 can effectively co-locate with CDH17 positive gastric cancer cells in zebrafish embryos. At the same time, E8 fused with the toxin PE38 showed excellent anti-tumor effects and significantly improved the survival rate of mice in cell-derived (CDX) and patient-derived xenotransplantation (PDX) models.

FAQ

1. What is the role of premade single domain antibody libraries in screening?

   A premade single domain antibody library is a large synthetic library containing a wide variety of antibody sequences, usually generated from natural immune libraries or by random combinations. These libraries are designed to screen high-affinity single-domain antibodies for rapid detection of specific antigens. In the screening process, antibodies that strongly interact with specific antigens can be selected from millions or even billions of candidate antibodies by using techniques such as phage display, yeast display, or other display techniques. This method speeds up the discovery of drug candidates, especially for rapid antibody development for new pathogens or rare targets.

2. What are the key considerations for premade single domain antibody libraries screening?

   The diversity and coverage of the antibody library are important factors that determine the success of screening. Ensuring sufficient diversity of sequences in the library can improve the probability of finding high affinity and high specific antibodies. Secondly, the display technology used in the screening process is also extremely important, and different display technologies have their own advantages and limitations. Choosing the appropriate technology can improve screening efficiency and success rate. The setting of screening conditions (such as antigen concentration, screening buffer conditions, etc.) will also affect the results. Too harsh conditions may lead to the loss of high affinity antibodies, while too loose conditions may not be able to effectively screen antibodies with the desired characteristics.

3. How to verify the antibody candidates screened by a premade single domain antibody library?

   First of all, the affinity test is carried out, and surface plasmon resonance (SPR) or biolayer interferometry (BLI) is usually used to evaluate the binding strength of the antibody to the antigen. Then, the specificity and biological activity of the antibody were verified by ELISA, flow cytometry, or immunofluorescence. In addition, it is important to conduct preclinical functional tests, such as inhibition tests, cytotoxicity tests or animal model studies, to evaluate the effect of antibodies in vivo. These verification steps are essential for confirming the practical application potential and safety of antibodies.

4. What are the differences between premade sdAb library screening and custom sdAb library screening?

   The main difference between premade sdAb library screening and custom sdAb library screening lies in the construction and application scope of the library. The premade library is pre-constructed and contains a wide range of antibodies, which is suitable for rapid screening and wide application, especially in the preliminary research stage or when the antigenic information is limited. On the contrary, the custom antibody library is specially designed and constructed for specific antigens or applications and can be optimized according to specific antigen characteristics and required antibody characteristics. Although custom libraries are more expensive and time-consuming to build, they usually provide better performance in terms of target specificity and functionality. Which screening method to choose depends on the specific needs of the project, including budget, time, and expected antibody characteristics.

5. What is the construction process of a premade single domain antibody library?

   The construction of premade single domain antibody libraries usually begins with the collection of antibody sequences from a wide range of sources, such as immune animals, human samples, or synthetic sequences. These sequences can be generated naturally or by random synthesis to ensure the diversity of antibodies in the library. The construction process involves the synthesis and cloning of DNA fragments encoding these sequences, and then inserting them into appropriate phage or cell expression vectors. Then, a large-scale transformation is carried out to create a sufficiently diverse library, often including billions to hundreds of billions of different clones. Finally, through sequence analysis and preliminary screening to verify the diversity and functionality of the library to ensure its efficiency and success rate in the follow-up high-throughput screening.

Resources

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