mRNA Display-based Antibody Affinity Maturation

Affinity is a key parameter of antibody drugs, which usually affects the function and efficacy of antibodies. In general, the antibody or humanized antibody generated by hybridoma cell technology has relatively high affinity, but this affinity may not be enough to meet the needs of therapeutic antibody. CD BioSciences provides antibody affinity maturation services by building a random mutation library and using mRNA display technology for high-throughput screening, ensuring that antibody affinity is improved several times, and fully meeting all your needs for affinity.

Introduction to Antibody Affinity Maturation

In general, antibodies are fully engineered to have optimized biological and physicochemical properties in terms of affinity, specificity and stability. The successful development of a variety of therapeutic monoclonal antibodies mainly requires the humanization of sequences and the maturation of affinity. The method of antibody affinity maturation has been widely studied and is still an active research field. This may be because the enhancement of antibody affinity may lead to higher biological activity, which in turn will reduce the injection dose, limit related side effects, and ultimately reduce the pharmaceutical cost. In general, therapeutic antibodies are expected to have a strong affinity of 1 nM or less to bind to their specific epitopes. Therefore, they usually go through one or more affinity maturation cycles to obtain the desired affinity.

Overview of affinity maturation.Fig. 1 Overview of affinity maturation. (Doria-Rose, et al., 2015)

mRNA Display for Antibody Affinity Maturation

So far, two methods for in vitro affinity maturation of antibodies have been developed, including random and targeted mutagenesis. After mutagenesis, an affinity screening procedure will be carried out through display technology to select the best mature antibody. The most common display systems include yeast two hybrid display, phage display, ribosome display and mRNA display. The combination strategy of antibody affinity maturation requires a relatively large library. The mRNA display system of cell-free system can display a larger library of up to 1014 members, and the constructed ternary complex is insensitive to reaction conditions through covalent bond connection, which can recognize antibodies with picomole affinity, showing great application potential in antibody affinity maturation.

Our Services

CD BioSciences has built a high-throughput antibody discovery platform based on mRNA display technology, which can provide antibody affinity maturity services for customers around the world. Our platform allows specific epitopes of antigen to be targeted through reasonable design strategies to generate high affinity antibodies, reducing the duration and cost of antibody engineering.

In the process of antibody affinity maturation in vitro, the selection of mutation region and how to introduce mutation are key issues, which are mainly divided into:

  • Mismatch PCR
  • DNA Reorganization
  • Chain Permutation
  • Directional Mutation

We can introduce multiple types of mutations in the design stage of the library and the affinity screening cycle according to the project needs of customers, and then obtain the target antibody whose affinity has been increased several times through multiple rounds of mRNA display.

Workflow of Antibody Affinity Maturation

Workflow of Antibody Affinity Maturation

CD BioSciences has many years of project development experience in antibody discovery. Based on the mRNA display technology platform, it can provide antibody affinity maturation services for customers. If you are interested in our service, please contact us for more details.

References

  1. Doria-Rose, N. A., & Joyce, M. G. (2015). Strategies to guide the antibody affinity maturation process. Current opinion in virology, 11, 137–147.
  2. Tabasinezhad, M., Talebkhan, Y., Wenzel, W., et al. (2019). Trends in therapeutic antibody affinity maturation: From in-vitro towards next-generation sequencing approaches. Immunology letters, 212, 106–113.
For Research Use Only. Not For Clinical Use.

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