Antibody Discovery Services

Synbio Technologies provides a broad range of DNA technologies to antibody services. Our technical platforms span all stages of antibody discovery by integrating “DNA Reading” (sequencing), “DNA Writing” (synthesis), “DNA Editing” (optimization), affinity mutation & humanization and others. In addition, we can deliver high-quality and cost-effective antibody expression, which helps to streamline your antibody/protein discovery.

Case Studies

Algorithm guided antibody design

Target antibody library construction

Bioinformatics analysis for antibody discovery

i. Algorithm guided antibody design of an antibody

Here we used a computational method to aid the de novo design of PXX antibody: The PXX structure was first modeled using a homology-based modeling method. We extracted the frameworks and complementary determinant regions (CDRs) from antibody structures. Using frameworks as templates, we assembled CDRs onto the frameworks to construct an antibody library, and the antibody structures were modeled from their homologous protein structures. Then, the antibodies were docked onto the antigen and ranked according to the interaction energy. A certain number of best antibody hits were selected and the antibody sequences were synthesized and screened to get potential antibodies.

PXX is an important negative immunoregulatory factor that was expressed by tumor cells and reduces the body’s immune response. Antibodies that bind to PXX and block its signaling pathway can be used as therapeutics for the treatment of carcinoma. In this case, our designed PXX antibody achieved an affinity of 10-11 M, which provided a novel anti-PXX antibody and candidate drugs. The time period and cost for antibody discovery were greatly reduced using this computational designing method.

 

Figure 1. Kd measurement by protein A based capture approach
Figure 2. Kd measurement by anti-human Fc based capture approach
Figure 3. Kd values of the antibody samples

ii. Antibody library construction for a target protein

For protein CXX, we implemented a novel approach to construct antibody library:  We extracted the frameworks and complementary determinant regions (CDRs) were extract from antibody structures and sequences. Using frameworks as templates, we assembled CDRs onto the frameworks to construct an antibody library, and the antibody structures were modeled from their homologous protein structures. The antibodies were docked onto the CXX protein and ranked according to the interaction energy. We then constructed an antibody library with around 106 antibody sequences according to the results. These sequences were synthesized and screened. The functionally active molecules were then obtained for further research.

Construction of antibody library for a protein
Figure 4. Round 3 & Round 4 ELISA screening of the antibody candidates

iii. Antibody discovery through bioinformatics analysis for Z virus infection

Blood samples were collected on the 6th and 13th day after Z virus infection. The antibody repertoire was sequenced. The NGS data was analyzed and clustered to get germline and CDR information. By comparing the results from two samples, we were able to select the top 50 differentially expressed antibodies. Then, the antibody genes were synthesized, expressed, and characterized in HEK cells. The active antibody to Z virus was screened using immune repertoire sequencing method.

 

Figure 5. The workflow of obtaining the viable antibodies against Z virus