Redwood was launched based on pioneering technology called “aldehyde tagging.” This technology was developed by Redwood’s co-founder and Scientific Advisory Board Chair, Carolyn Bertozzi, Ph.D. at the University of California, Berkeley, and her research team, including David Rabuka, Ph.D., Company co-founder, President and Chief Scientific Officer. An aldehyde tag functions as a unique chemical site on the surface of a protein that can be selectively modified through aldehyde specific chemistry.
The Problem
Drug conjugates in development primarily rely on traditional chemical conjugation targeting native protein amino acid side chains. This approach does not provide good control over cargo placement and loading given dependence on a protein’s natural amino acid sequence, which limits conjugate optimization. Moreover, native amino acid side chain chemistry is associated with poor reproducibility, resulting in heterogeneous drug mixtures with variable potency and toxicity.
Genetic fusion technology also has been employed to create conjugates through the recombinant fusion of therapeutic peptideswith protein carriers. This approach can limit conjugatepotencygiven fusion of the peptide payloadthrough its termini, inhibiting payload orientation optimization and loading.
The Redwood Solution
Redwood's technology employs an “all natural” amino acid sequence inserted site specifically into protein DNA. A naturally occurring enzyme, the formylglycine-generating enzyme (“FGE”), recognizes and acts specifically on this sequence, creating an unusual aldehyde-bearing formylglycine (FGly) residue. FGly provides a unique chemical functionality in the modified protein that can be selectively reacted with aldehyde-specific reagents, allowing for a myriad of site-specific modifications with precise chemical control.
Aldehyde tags can be placed into any protein of interest, including mammalian cell produced proteins, with ease and high efficiency. Multiple tags can be used for cargo loading, while preserving the modified protein’s natural structure and biological activity. In addition, the aldehyde conjugation chemistry employed affords flexibility over cargo orientation and has good reproducibility, resulting in homogenous compounds. Control over cargo placement, number and orientation as well as good conjugation efficiency, enable the creation of combinatorial conjugate libraries for identification of superior antibody-drug conjugates and peptide therapeutics.
