Intein mediated high throughput screening for bispecific antibodies

Area of Science:

• Biotechnology
• Immunology
• Pharmaceutical Sciences

Background:

• Bispecific antibodies offer advanced therapeutic capabilities beyond monospecific antibodies.
• Current screening methods for bispecific antibodies are limited in evaluating the vast number of potential combinations, leading to extended development times.
• High-throughput screening (HTS) for small molecules and conventional antibodies is well-established, but lacks efficiency for bispecific antibody discovery.

Purpose of the Study:

• To develop a novel combinatorial screening approach for bispecific IgG-like antibodies.
• To overcome the limitations of current screening methodologies in terms of scale and combinatorial space coverage.
• To enable rapid, automated, and efficient high-throughput screening of bispecific antibody candidates.

Main Methods:

• Utilized a protein trans-splicing reaction mediated by the split intein Npu DnaE.
• Reconstituted antibody fragments within the hinge region in vitro.
• Developed a fully automated, one-pot antibody reconstitution process.

Main Results:

• The novel method allows for rapid antibody reconstitution and demonstrates biological activity in various assays.
• The approach significantly expands the screening space for bispecific antibody combinations.
• The technology is suitable for automated functional and combinatorial high-throughput screening.

Conclusions:

• The presented protein trans-splicing method offers a powerful tool for bispecific antibody discovery.
• This innovation addresses the limitations in current bispecific antibody screening, facilitating faster development of novel therapeutics.
• The automated, high-throughput screening approach accelerates the evaluation of diverse bispecific antibody architectures.