ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2020
Selection of a Full Agonist Combinatorial Antibody that Rescues Leptin Deficiency In Vivo.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 13 citations in OpenAlex.
- Technologies for Monoclonal Antibody Discovery and Development.International journal of molecular sciences · 2025Review
- Advances in the structure-based design of protein vaccines for respiratory infectious diseases.Computational and structural biotechnology journal · 2025Review
- Replenishment of mitochondrial NaMaterials today. Bio · 2024Article
- Selection of Leptin Surrogates by a General Phenotypic Screening Method for Receptor Agonists.Biomolecules · 2024Article
- Potent NTD-Targeting Neutralizing Antibodies against SARS-CoV-2 Selected from a Synthetic Immune System.Vaccines · 2023Article
- Structural insights into the mechanism of leptin receptor activation.Nature communications · 2023Article
- A Historical Review of Brain Drug Delivery.Pharmaceutics · 2022Review
- Article
- Antibody Libraries as Tools to Discover Functional Antibodies and Receptor Pleiotropism.International journal of molecular sciences · 2021Review
- Selection of a Full Agonist Combinatorial Antibody that Rescues Leptin Deficiency In Vivo.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2020Article
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Growth factor deficiency in adulthood constitutes a distinct clinical syndrome with significant morbidities including abnormal body composition, reduced energy, affective disturbances, dyslipidemia, and increased cardiovascular risk. Protein replacement therapies using recombinant proteins or enzymes represent the only approved treatment. Combinatorial antibodies have shown great promise as a new class of therapeutic molecules because they act as "mechanism-based antibodies" with both agonist and antagonist activities. Using leptin, a key hormone in energy metabolism, as an example, a function-guided approach is developed to select combinatorial antibodies with high potency and full agonist activity that substitute natural growth factors in vivo. The identified antibody shows identical biochemical properties and cellular profiles as leptin, and rescues leptin-deficiency in ob/ob mice. Remarkably, the antibody activates leptin receptors that are otherwise nonfunctional because of mutations (L372A and A409E). Combinatorial antibodies have significant advantages over recombinant proteins for chronical usage in terms of immunological tolerance and biological stability.
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Registered trials
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