March 5, 2025
Deep mutational learning for the selection of therapeutic antibodies resistant to the evolution of Omicron variants of SARS-CoV-2
Design and construction of a high-distance Omicron BA.1 RBD library A mutagenesis library was constructed based on BA.1, covering the entire 201 amino acid RBD region (positions 331–531 of SARS-CoV-2 S protein). To maximize the interrogated RBD sequence space, the library design was entirely synthetic and unbiased, as it did not consider evolutionary data or previous experimental findings. For the construction of the library, the RBD sequence was split into 11–12 fragments, each with an approximate length of 48 nucleotides (Supplementary Table 1). For a fragment of average length, 137 different single-stranded oligonucleotides (ssODN) were designed, where each ssODN had