Single-Domain Antibodies—Novel Tools to Study and Treat Allergies

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(14), P. 7602 - 7602

Published: July 11, 2024

IgE-mediated allergies represent a major health problem in the modern world. Apart from allergen-specific immunotherapy (AIT), only disease-modifying treatment, researchers focus on biologics that target different key molecules such as allergens, IgE, or type 2 cytokines to ameliorate allergic symptoms. Single-domain antibodies, nanobodies, are newcomers biotherapeutics, and their huge potential is being investigated various research fields since discovery 30 years ago. While they dominantly applied for theranostics of cancer treatment infectious diseases, nanobodies have become increasingly substantial allergology over last decade. In this review, we discuss prerequisites consider be important generating useful nanobody-based drug candidates treating allergies. We further summarize available data used allergen monitoring detection probes therapeutic approaches. reflect limitations addressed during development process, vivo half-life immunogenicity. Finally, speculate about novel application formats allergy might future.

Language: Английский

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AI-enabled Alkaline-resistant Evolution of Protein to Apply in Mass Production

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 8, 2024

Abstract Artificial intelligence (AI) models have been used to study the compositional regularities of proteins in nature, enabling it assist protein design improve efficiency engineering and reduce manufacturing cost. However, industrial settings, are often required work extreme environments where they relatively scarce or even non-existent nature. Since such almost absent training datasets, is uncertain whether AI model possesses capability evolving adapt conditions. Antibodies crucial components affinity chromatography, hoped remain active at most cannot tolerate. In this study, we applied an advanced large language (LLM), Pro-PRIME model, alkali resistance a representative antibody, VHH antibody capable binding growth hormone. Through two rounds design, ensured that selected mutant has enhanced functionality, including higher thermal stability, pH stronger affinity, thereby validating generalized LLM meeting specific demands. To best our knowledge, first LLM-designed product, which successfully mass production.

Language: Английский

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Extending linker sequences between antigen-recognition modules provides more effective production of bispecific nanoantibodies in the periplasma of <i>E. coli</i>

Биохимия, Journal Year: 2024, Volume and Issue: 89(5), P. 920 - 928

Published: Nov. 14, 2024

The use of technology for the production single-domain antibodies (NANOBODY® molecules, also referred to as nanoantibodies, nAb, or molecules based on other stable protein structures) and their derivatives solve current problems in biomedicine is becoming increasingly popular. Indeed, format one small, highly soluble with a structure, fully functional terms specific recognition, very convenient module creating multivalent, bi-/oligo-specific genetically engineered targeting structures. nAb periplasm E. coli bacterium fairly universal way obtain analytical quantities initial study properties these selection most promising options. situation more complicated bi- multivalent initially selected nAbs under same conditions. In this work, extended linker sequences (52 86 aa) between antigen-recognition modules cloned expression constructs were developed applied order increase efficiency bispecific nanoantibodies (bsNB) bacteria. Three variants model bsNBs described produced bacteria isolated form preservation functionality all domains. If earlier our attempts produce bsNB traditional linkers no longer than 30 aa unsuccessful, used here provided significantly efficient bsNB, comparable original monomeric nAbs. elongated can presumably be useful increasing similar

Language: Английский

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AI-enabled Alkaline-resistant Evolution of Protein to Apply in Mass Production

Published: Dec. 2, 2024

Artificial intelligence (AI) models have been used to study the compositional regularities of proteins in nature, enabling it assist protein design improve efficiency engineering and reduce manufacturing cost. However, industrial settings, are often required work extreme environments where they relatively scarce or even non-existent nature. Since such almost absent training datasets, is uncertain whether AI model possesses capability evolving adapt conditions. Antibodies crucial components affinity chromatography, hoped remain active at most cannot tolerate. In this study, we applied an advanced large language (LLM), Pro-PRIME model, alkali resistance a representative antibody, VHH antibody capable binding growth hormone. Through two rounds design, ensured that selected mutant has enhanced functionality, including higher thermal stability, pH stronger affinity, thereby validating generalized LLM meeting specific demands. To best our knowledge, first LLM-designed product, which successfully mass production.

Language: Английский

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Molekulares Design von Nanobodies als Werkzeuge in der Allergologie: Diagnostik und mehr

Allergo Journal, Journal Year: 2023, Volume and Issue: 32(7), P. 29 - 40

Published: Oct. 31, 2023

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