Protelica has developed a number of patented DNA mutagenesis technologies for protein affinity maturation: Walk-Through Mutagenesis™ (WTM), Look-Through Mutagenesis™ (LTM) and Combinatorial Beneficial Mutation™ (CBM). The processes use a rational, chemistry-based approach (amino acid side chains) to build “intelligent” libraries and develop protein analogs with improved affinities. Traditional DNA mutagenesis approaches involve techniques such as random mutagenesis, saturation mutagenesis, error prone PCR, and gene shuffling. These strategies are inherently stochastic and often require the construction of exceedingly large libraries to comprehensively explore sufficient sequence diversity. Creating these exceedingly large synthetic libraries, however, often results in a high percentage of unproductive variants, leading to candidate screens that are inefficient in both cost and time.
In contrast, our mutagenesis technologies (WTM, LTM, and CBM) are based on a defined DNA synthesis methodology that builds structured, motif-oriented, “intelligent” libraries. The oligonucleotides are designed to precisely execute codon-by-codon modifications and to introduce selected target amino acids systematically and comprehensively into selected positions of the protein. This approach creates protein libraries that comprehensively cover meaningful protein space in a compact design. Our libraries are smaller, very focused, and highly efficient. Moreover, our technology is the only one capable of exploring large protein sequences and producing sequence-function information. We believe that Protelica’s patented mutagenesis technologies produce the highest quality “universal” protein libraries that, in turn, allow for rapid selection of binders to potential targets. Protelica’s Intelligent Mutagenesis is covered by numerous patents and patent applications worldwide.