Design, Construction, and Validation of a Yeast-Displayed Chemically Expanded Antibody Library.

display technologies, exemplified by phage and yeast display, have emerged as powerful platforms for antibody discovery and engineering. However, the identification of antibodies that disrupt target functions beyond binding remains a challenge. In particular, there are very few strategies that support identification and engineering of either protein-based irreversible binders or inhibitory enzyme binders.

Engineering Proteins Containing Noncanonical Amino Acids on the Yeast Surface.

Yeast display has been used to advance many critical research areas, including the discovery of unique protein binders and biological therapeutics. In parallel, noncanonical amino acids (ncAAs) have been used to tailor antibody-drug conjugates and enable discovery of therapeutic leads. Together, these two technologies have allowed for generation of synthetic antibody libraries, where the introduction of ncAAs in yeast-displayed proteins allows for library screening for therapeutically relevant targets.

Intracellular Delivery of Antibodies for Selective Cell Signaling Interference.

Many intracellular signaling events remain poorly characterized due to a general lack of tools to interfere with "undruggable" targets. Antibodies have the potential to elucidate intracellular mechanisms via targeted disruption of cell signaling cascades because of their ability to bind to a target with high specificity and affinity. However, due to their size and chemical composition, antibodies cannot innately cross the cell membrane, and thus access to the cytosol with these macromolecules has been limited.