The Library of Libraries: a Next-Generation Approach to Discover New Antibody Medicines

Have you ever heard of a “Library for Libraries”? You’re probably thinking, “hmm, sounds like a lot of books.” But in fact, the Twist Biopharma Library of Libraries is a collection of precisely crafted DNA variant libraries for rapid and effective antibody discovery, with applications from new therapeutics to cutting edge diagnostics. These Libraries are also opening an entirely new set of sequence space, allowing researchers to focus in on difficult-to-drug targets, like GPCR’s and Ion Channels, giving new hope that treatments for complex and rare diseases may soon be within reach.

Pharmaceutical and biotechnology companies, including Takeda, are already leveraging the Library of Libraries in their antibody discovery pipelines. In a recent and highly relevant example, Twist Biopharma screened the Library of Libraries against human ACE2 and SARS-CoV-2 spike protein to find potently neutralizing candidate antibodies against the SARS-CoV-2 strain of coronavirus in under 4 weeks.

How the Library of Libraries accelerates antibody discovery pipelines

Each library within the Library of Libraries contains over 10 billion human antibody sequences utilizing different antibody fragment scaffolds, as well as different sources of human antibody repertoires. Libraries are precisely designed based solely on effective sequence space and to match sequences that occur in the human body, removing confounding or redundant sequences from screens. “Incorporating such scale and diversity means each screen performed with the Library of Libraries has a far greater likelihood to find high-affinity binding antibodies compared to traditional methods,” states Dr. Emily Leproust, CEO of Twist Bioscience.

Writing the Future Of Biologics

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Twist Biopharma, a division of Twist Bioscience, has recently launched 16 libraries, making up the current and ever growing library of libraries portfolio. Customers aiming to identify candidate antibody therapeutics can license these libraries for their own use, or partner with Twist Biopharma who can take on the antibody discovery process. Either way, customers can take advantage of Twist Biopharma’s decades of expertise to accelerate and simplify their discovery pipelines.

“Our Library of Libraries contains several pre-constructed and validated libraries against many high-value targets,” commented Emily. “We built this with one intention: to build the most comprehensive and robust antibody discovery platform on the market.”

Access to such libraries is unprecedented in the antibody discovery market and is only possible due to the high throughput synthesis capabilities of Twist Bioscience. Twist Bioscience’s silicon-based DNA synthesis platform can generate millions of oligonucleotides in a single run. Those oligonucleotides then get stitched together to make longer gene fragments, containing the precise modifications specified by the library designer. On this foundation, Twist Biopharma can create synthetic antibody libraries that contain immense sequence diversity while avoiding biases and errors that can affect screen efficiency, including insertions, deletions, or mutations.

Customers interested in rapid and effective antibody discovery for high-value targets are able to either license the Library of Libraries from Twist Biopharma or partner directly with Twist Biopharma to outsource lead discovery fully. “Twist Biopharma’s screens are conducted by phage display. This technology allows us to screen against almost any form of antigen, including proteins, cells, and peptides. It also eliminates the need for immunization and hybridoma protocols, and works seamlessly with human or human-like antibodies,” says Emily. 

Twist Biopharma’s Library of Libraries offers an exciting opportunity for drug developers to look deeper at challenging targets. Until now, many targets have been considered difficult-to-drug, and discovery research in these fields has proven technically challenging, time-consuming, and expensive. By helping to remove barriers to drug discovery with the Library of Libraries, Twist Biopharma hopes to enable new, life-changing therapeutics.

Are you interested in working with Twist Biopharma on your next significant discovery? Fill out an inquiry form now.