Creating a Drosophila antibody library

PISCATAWAY, N.J.—GenScript, the world’s leading gene synthesis provider, disclosed today that it will provide funding and DNA synthesis expertise toward a project at Harvard University to generate the first comprehensive, renewable library of Drosophila recombinant antibodies. Proposed by Norbert Perrimon, Ph.D., the James Stillman professor of Developmental Biology at Harvard Medical School and a Howard Hughes Medical Institute investigator, the project aims to promote the understanding of molecular mechanisms of disease progression. More specifically, it will give researchers access to novel tools for assessing CRISPR efficiency.

Perrimon, the principal investigator of the project, has more than 30 years of experience in the fields of developmental genetics, signal transduction and genomics. Through developing novel large-scale RNAi, CRISPR and proteomic methods, he and his team have been able to identify key signaling molecules involved in homeostasis and tissue remodeling in Drosophila. These valuable resources, including the upcoming antibody resource, are publicly shared with scientists across the globe to allow systematic interrogation of the genome and proteome of this widely used laboratory model.

According to Cedric Wu, Ph.D., GenScript senior director of R&D, Perrimon’s successful track record and contributions to Drosophila research and his unique goals for this project were key in choosing to fund it. “The aim of this project, in enabling further research by many scientists within and beyond the fly’s research community, is well aligned with our goal,” Wu said.

Out of the total number of proteins encoded by the ~14,000 Drosophila protein-coding genes, fewer than 400 renewable antibody reagents, i.e. recombinant monoclonal antibodies, are currently annotated for this fly’s proteins. As stated in Perrimon’s project proposal, a synthetic library of antibodies generated with advanced recombinant technologies in an optimized fly cell line provides a non-animal platform for generating antibodies that not only have desired post-translational modifications, but also are reproducible and renewable.

The foundation of this project is to have antibody recognition sequences precisely cloned into appropriate expression vectors and protein backbones. GenScript’s track record in delivering thousands of similar projects will help build this foundation for Perrimon’s team before expression in an insect vector and selection by a synthetic antibody library. In the first phase of this project, over 100 antibodies will be generated, with scaling up to more than 3,000 antibodies in the next phase.

Perrimon’s constructs will be codon-optimized with OptimumGene, GenScript’s proprietary codon optimization tool, and deposited in GenScript’s not-for-profit MolecularCloud repository for access by the scientific community worldwide. GenScript says it intends to support more projects in the future that will have a significant impact on improving the health of humans directly, and other organisms and the environment indirectly.