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RAMIHM generates fully human monoclonal antibodies by rapid mRNA immunization of humanized mice and BCR-seq.
Ren, Ping; Peng, Lei; Yang, Luojia; Suzuki, Kazushi; Fang, Zhenhao; Renauer, Paul A; Lin, Qianqian; Bai, Meizhu; Li, Tongqing; Clark, Paul; Klein, Daryl; Chen, Sidi.
  • Ren P; Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA; System Biology Institute, Yale University, West Haven, CT 06520, USA; Center for Cancer Systems Biology, Yale University, West Haven, CT 06520, USA.
  • Peng L; Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA; System Biology Institute, Yale University, West Haven, CT 06520, USA; Center for Cancer Systems Biology, Yale University, West Haven, CT 06520, USA.
  • Yang L; Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA; System Biology Institute, Yale University, West Haven, CT 06520, USA; Center for Cancer Systems Biology, Yale University, West Haven, CT 06520, USA.
  • Suzuki K; Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA; System Biology Institute, Yale University, West Haven, CT 06520, USA; Center for Cancer Systems Biology, Yale University, West Haven, CT 06520, USA.
  • Fang Z; Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA; System Biology Institute, Yale University, West Haven, CT 06520, USA; Center for Cancer Systems Biology, Yale University, West Haven, CT 06520, USA.
  • Renauer PA; Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA; System Biology Institute, Yale University, West Haven, CT 06520, USA; Center for Cancer Systems Biology, Yale University, West Haven, CT 06520, USA; Molecular Cell Biology, Genetics, and Development Program, Yale U
  • Lin Q; Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA; System Biology Institute, Yale University, West Haven, CT 06520, USA; Center for Cancer Systems Biology, Yale University, West Haven, CT 06520, USA.
  • Bai M; Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA; System Biology Institute, Yale University, West Haven, CT 06520, USA; Center for Cancer Systems Biology, Yale University, West Haven, CT 06520, USA.
  • Li T; Department of Pharmacology, Yale University, New Haven, CT 06520, USA; Cancer Biology Institute, Yale University, New Haven, CT 06520, USA.
  • Clark P; Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA; System Biology Institute, Yale University, West Haven, CT 06520, USA; Center for Cancer Systems Biology, Yale University, West Haven, CT 06520, USA.
  • Klein D; Department of Pharmacology, Yale University, New Haven, CT 06520, USA; Cancer Biology Institute, Yale University, New Haven, CT 06520, USA.
  • Chen S; Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA; System Biology Institute, Yale University, West Haven, CT 06520, USA; Center for Cancer Systems Biology, Yale University, West Haven, CT 06520, USA; Molecular Cell Biology, Genetics, and Development Program, Yale U
Cell Chem Biol ; 30(1): 85-96.e6, 2023 Jan 19.
Article in English | MEDLINE | ID: covidwho-2177358
ABSTRACT
As a clinical vaccine, lipid nanoparticle (LNP) mRNA has demonstrated potent and broad antibody responses, leading to speculation about its potential for antibody discovery. Here, we developed RAMIHM, a highly efficient strategy for developing fully human monoclonal antibodies that employs rapid mRNA immunization of humanized mice followed by single B cell sequencing (scBCR-seq). We immunized humanized transgenic mice with RAMIHM and generated 15 top-ranked clones from peripheral blood, plasma B, and memory B cell populations, demonstrating a high rate of antigen-specificity (93.3%). Two Omicron-specific neutralizing antibodies with high potency and one broad-spectrum neutralizing antibody were discovered. Furthermore, we extended the application of RAMIHM to cancer immunotherapy targets, including a single transmembrane protein CD22 and a multi-transmembrane G protein-coupled receptor target, GPRC5D, which is difficult for traditional protein immunization methods. RAMIHM-scBCR-seq is a broadly applicable platform for the rapid and efficient development of fully human monoclonal antibodies against an assortment of targets.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Immunization / Antibodies, Monoclonal Type of study: Prognostic study Topics: Vaccines / Variants Limits: Animals / Humans Language: English Journal: Cell Chem Biol Year: 2023 Document Type: Article Affiliation country: J.chembiol.2022.12.005

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Immunization / Antibodies, Monoclonal Type of study: Prognostic study Topics: Vaccines / Variants Limits: Animals / Humans Language: English Journal: Cell Chem Biol Year: 2023 Document Type: Article Affiliation country: J.chembiol.2022.12.005