Welcome to the Recombinant Antibody Network

@article{pmid42757708,

title = {Strategy for modular assembly of tetravalent, multispecific antibodies},

author = {Evan Mallette and Levi L Blazer and Craig A Hokanson and Chao Chen and Julia Garcia Perez and Alevtina Pavlenco and Lynda Ploder and Alexander U Singer and Michael D L Suits and Sunil Bhakta and Jagath R Junutula and Jarrett J Adams and Sachdev S Sidhu},

doi = {10.1002/pro.70797},

issn = {1469-896X},

year  = {2026},

date = {2026-10-01},

urldate = {2026-10-01},

journal = {Protein Sci},

volume = {35},

number = {10},

pages = {e70797},

abstract = {Multispecific, multivalent antibodies (Abs) are a burgeoning class of drugs that dramatically expand the pharmacological repertoire beyond traditional therapeutic Abs. Here, we present a simple, modular approach to developing multispecific, multivalent Abs based on a Fab-phage library with a single light chain. Using this library, we created three Abs targeting unique sites on programmed death-ligand 1 (PD-L1) and another antibody targeting CD30. Biophysical and cellular characterization of these Abs demonstrated their functional equivalence to clinically relevant Abs targeting PD-L1 or CD30. We then combined these paratopes into a series of bispecific, tetravalent, triparatopic Abs that retained the functionality of the parental Abs. Structural analysis of each of the Abs in complex with their cognate antigens demonstrated the adaptability of the common light chain to form diverse paratopes with an array of distinct heavy chains.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid42290195,

title = {Clarifying Frizzled 2 function in development through genetically validated mouse models},

author = {Megan N Michalski and Cassandra R Diegel and Zhendong A Zhong and Maddison E Marshall and Gabrielle E Foxa Wiartalla and Payton D Stevens and Kelly Suino-Powell and Levi L Blazer and Jarrett J Adams and Karsten Melcher and Sachdev S Sidhu and Stephane Angers and Bart O Williams},

doi = {10.1242/dmm.052410},

issn = {1754-8411},

year  = {2026},

date = {2026-07-01},

urldate = {2026-07-01},

journal = {Dis Model Mech},

volume = {19},

number = {7},

abstract = {Wnt receptors of the Frizzled (Fzd) family are widely considered to exhibit substantial functional redundancy, complicating efforts to therapeutically target individual receptors. Fzd2 was believed to be functionally redundant with Fzd1 and Fzd7, based on previously published global knockout mouse studies. By contrast, homozygosity for a Fzd2 global knockout mouse allele developed by the International Mouse Phenotype Consortium (IMPC) has been reported to cause embryonic lethality, suggesting that Fzd2 is critical for early embryonic development. If global deletion of Fzd2 leads to early lethality, conditional deletion models are necessary to identify tissue-specific phenotypes. We found that a previously published Fzd2 conditional deletion model does not eliminate Fzd2. We have generated a new conditional model to address the contradictory previous studies and allow tissue-specific studies of Fzd2. We successfully inserted two loxP sites around the Fzd2 gene and confirmed that subsequent Cre-mediated recombination creates a Fzd2 null allele. Global deletion of Fzd2 in this model does not cause embryonic lethality while limb-specific deletion causes limb shortening. This work supports the hypothesis that Fzd2 regulates limb development and emphasizes the importance of thoroughly validating newly generated mouse models.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid42538903,

title = {A  designed enzyme for photo-proximity labeling of E3 ligase neighborhoods in live cells},

author = {Nam Hyeong Kim and Zhi Lin and Sangwon Nam and Danielle L Swaney and Nevan Krogan and Yong Ho Kim and Michael J Therien and William F DeGrado and James A Wells},

doi = {10.64898/2026.07.22.739993},

issn = {2692-8205},

year  = {2026},

date = {2026-07-01},

urldate = {2026-07-01},

journal = {bioRxiv},

abstract = {Photocatalytic proximity labeling proteomics (photo-PLP) has emerged as a powerful technology for rapid capture of protein interactomes in situ. Typically, photo-PLP relies on chemical conjugation of the photocatalyst to the target of interest which creates practical challenges for derivatized photocatalyst synthesis and bioconjugation specificity. Integrating the precision of genetically encodable enzymes with the versatility of chemically defined photocatalysts provides a modular approach to further expand the scope of neighborhood mapping. Here, we present EYClamp, a  designed proximity labeling enzyme harnessing the off-the-shelf photocatalyst Eosin Y (EY) as a cofactor. Using a domain-swapped dimer architecture, we designed a scaffold that binds EY with high affinity (   = 10 nM) and lengthens its triplet excited-state lifetime by 29-fold. EYClamp enables efficient, multi-scale photocatalytic proximity labeling in live cells with aryl-diazirine-, aryl-azide- and phenol-biotin. We genetically fused EYClamp to a panel of six important E3 ligases. Using EYClamp, we identified over 1,500 candidate neighbors for KEAP1, MDM2, ASB7 and STUB1, providing a broad and unbiased view of these important neighborhoods. Critical functional networks were revealed including ASB7 engagement with HP1a/CUL5 complex for heterochromatin remodeling. Our EYClamp provides a genetically encodable "plug-and-play" solution for photo-PLP interactome discovery of the large family of E3 ligases and establishes domain-swapping as a promising strategy for  photoenzyme design.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}