AnaptysBio's antibody pipeline has been developed using its proprietary somatic
hypermutation, or SHM platform, which uses in vitro SHM for antibody discovery and is designed to replicate key features of the human immune system to overcome the limitations of competing antibody discovery technologies.
In mature B-cell neoplasms, characteristic translocations involving the immunoglobulin loci originate from aberrant V(D)J recombination, class switch recombination, or activation-induced cytidine deaminase-mediated somatic
hypermutation. Although most of the breakpoints in the immunoglobulin loci occur at defined positions, those in the partner genes can occur anywhere over large areas of extragenic, nontranscribed sequences.
Inactivation of MMR protein function is well known to have numerous biological consequences, including genome instability, resistance to DNA damaging agents including chemotherapeutic drugs, [18] altered class switch recombination and somatic
hypermutation of immunoglobulin genes, [19] emergence of pathogenic bacteria, infertility, promotes TNR expansion [20,21] and increased susceptibility to cancer.
We use a neighborhood operator called
hypermutation, inspired from [24].
Han et al., "Directed evolution using dCas9-targeted somatic
hypermutation in mammalian cells," Nature Methods, vol.
Nones et al., "
Hypermutation in pancreatic cancer," Gastroenterology, vol.
Zuhlke-Jenisch et al., "Chromosomal translocations fusing the BCL6 gene to different partner loci are recurrent in primary central nervous system lymphoma and may be associated with aberrant somatic
hypermutation or defective class switch recombination," Journal of Neuropathology & Experimental Neurology, vol.
The algorithm comprises five immune operators: cloning operator,
hypermutation operator, suppression operator, selection and receptor editing operator, and memory updating operator, and one genetic operator: crossover operator.
Thus, B cells undergo somatic
hypermutation and immunoglobulin class-switching recombination as a part of the GC reactions mediated by the activation-induced cytidine deaminase (AID) enzyme [92].
Gould, "Local somatic
hypermutation and class switch recombination in the nasal mucosa of allergic rhinitis patients," The Journal of Immunology, vol.
The clones then undergo somatic
hypermutation and produce antibodies that are specific to the invading antigen.