@article{tiruthani_cruz-teran_chan_ma_mcsweeney_wolf_yuan_poon_chan_botta_et al._2024, title={Engineering a "muco-trapping" ACE2-immunoglobulin hybrid with picomolar affinity as an inhaled, pan-variant immunotherapy for COVID-19}, ISSN={["2380-6761"]}, DOI={10.1002/btm2.10650}, abstractNote={Abstract}, journal={BIOENGINEERING & TRANSLATIONAL MEDICINE}, author={Tiruthani, Karthik and Cruz-Teran, Carlos and Chan, Jasper F. W. and Ma, Alice and Mcsweeney, Morgan and Wolf, Whitney and Yuan, Shoufeng and Poon, Vincent K. M. and Chan, Chris C. S. and Botta, Lakshmi and et al.}, year={2024}, month={Feb} }
 @article{mcsweeney_stewart_richardson_kang_park_kim_tiruthani_wolf_schaefer_kumar_et al._2022, title={Stable nebulization and muco-trapping properties of regdanvimab/IN-006 support its development as a potent, dose-saving inhaled therapy for COVID-19}, ISSN={["2380-6761"]}, DOI={10.1002/btm2.10391}, abstractNote={Abstract}, journal={BIOENGINEERING & TRANSLATIONAL MEDICINE}, author={McSweeney, Morgan and Stewart, Ian and Richardson, Zach and Kang, Hyunah and Park, Yoona and Kim, Cheolmin and Tiruthani, Karthik and Wolf, Whitney and Schaefer, Alison and Kumar, Priya and et al.}, year={2022}, month={Aug} }
 @article{shrestha_schaefer_zhu_saada_jacobs_chavez_omsted_cruz-teran_vaca_vincent_et al._2021, title={Engineering sperm-binding IgG antibodies for the development of an effective nonhormonal female contraception}, volume={13}, ISSN={["1946-6242"]}, DOI={10.1126/scitranslmed.abd5219}, abstractNote={Many women risk unintended pregnancy because of medical contraindications or dissatisfaction with contraceptive methods, including real and perceived side effects associated with the use of exogenous hormones. We pursued direct vaginal delivery of sperm-binding monoclonal antibodies (mAbs) that can limit progressive sperm motility in the female reproductive tract as a strategy for effective nonhormonal contraception. Here, motivated by the greater agglutination potencies of polyvalent immunoglobulins but the bioprocessing ease and stability of immunoglobulin G (IgG), we engineered a panel of sperm-binding IgGs with 6 to 10 antigen-binding fragments (Fabs), isolated from a healthy immune-infertile woman against a unique surface antigen universally present on human sperm. These highly multivalent IgGs (HM-IgGs) were at least 10- to 16-fold more potent and faster at agglutinating sperm than the parent IgG while preserving the crystallizable fragment (Fc) of IgG that mediates trapping of individual spermatozoa in mucus. The increased potencies translated into effective (>99.9%) reduction of progressively motile sperm in the sheep vagina using as little as 33 μg of the 10-Fab HM-IgG. HM-IgGs were produced at comparable yields and had identical thermal stability to the parent IgG, with greater homogeneity. HM-IgGs represent not only promising biologics for nonhormonal contraception but also a promising platform for engineering potent multivalent mAbs for other biomedical applications.}, number={606}, journal={SCIENCE TRANSLATIONAL MEDICINE}, author={Shrestha, Bhawana and Schaefer, Alison and Zhu, Yong and Saada, Jamal and Jacobs, Timothy M. and Chavez, Elizabeth C. and Omsted, Stuart S. and Cruz-Teran, Carlos A. and Vaca, Gabriela Baldeon and Vincent, Kathleen and et al.}, year={2021}, month={Aug} }
 @article{schaefer_lai_2021, title={The biophysical principles underpinning muco-trapping functions of antibodies}, ISSN={["2164-554X"]}, DOI={10.1080/21645515.2021.1939605}, abstractNote={ABSTRACT In addition to the classical immunological functions such as neutralization, antibody-dependent cellular cytotoxicity, and complement activation, IgG antibodies possess a little-recognized and under-utilized effector function at mucosal surfaces: trapping pathogens in mucus. IgG can potently immobilize pathogens that otherwise readily diffuse or actively swim through mucus by forming multiple low-affinity bonds between the array of pathogen-bound antibodies and the mucin mesh. Trapping in mucus can exclude pathogens from contacting target cells, and facilitate their rapid elimination by natural mucus clearance mechanisms. Despite the fact that most infections are transmitted at mucosal surfaces, this muco-trapping effector function has only been revealed within the past decade, with the evidence to date suggesting that it is a universal effector function of IgG-Fc capable of immobilizing both viral and highly motile bacterial pathogens in all major mucosal secretions. This review provides an overview of the current evidence for Fc-mucin crosslinking as an effector function for antibodies in mucus, the mechanism by which the accumulation of weak Fc-mucin bonds by IgG bound to the surface of a pathogen can result in immobilization of antibody-pathogen complexes, and how trapping in mucus can contribute to protection against foreign pathogens.}, journal={HUMAN VACCINES & IMMUNOTHERAPEUTICS}, author={Schaefer, Alison and Lai, Samuel K.}, year={2021}, month={Jun} }