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Single-domain antibody delivery using an mRNA platform protects against lethal doses of botulinum neurotoxin Aстатья
Статья опубликована в высокорейтинговом журнале
Статья опубликована в журнале из списка Web of Science и/или Scopus- Авторы: Panova Eugenia A., Kleymenov Denis A., Shcheblyakov Dmitry V., Bykonia Evgeniia N., Mazunina Elena P., Dzharullaeva Alina S., Zolotar Anastasia N., Derkaev Artem A., Esmagambetov Ilias B., Sorokin Ivan I., Usachev Evgeny V., Noskov Anatoly N., Ivanov Igor A., Zatsepin Timofei S., Dmitriev Sergey E., Gushchin Vladimir A., Naroditsky Boris S., Logunov Denis Y., Gintsburg Alexander L.
- Журнал: Frontiers in immunology
- Том: 14
- Год издания: 2023
- Издательство: Frontiers Research Foundation]
- Местоположение издательства: [Lausanne, Switzerland
- Номер статьи: 1098302
- DOI: 10.3389/fimmu.2023.1098302
- Аннотация: Single-domain antibodies (sdAbs, VHHs, or nanobodies) are a promising tool for the treatment of both infectious and somatic diseases. Their small size greatly simplifies any genetic engineering manipulations. Such antibodies have the ability to bind hard-to-reach antigenic epitopes through long parts of the variable chains, the third complementarity-determining regions (CDR3s). VHH fusion with the canonical immunoglobulin Fc fragment allows the Fc-fusion single-domain antibodies (VHH-Fc) to significantly increase their neutralizing activity and serum half-life. Previously we have developed and characterized VHH-Fc specific to botulinum neurotoxin A (BoNT/A), that showed a 1000-fold higher protective activity than monomeric form when challenged with five times the lethal dose (5 LD50) of BoNT/A. During the COVID-19 pandemic, mRNA vaccines based on lipid nanoparticles (LNP) as a delivery system have become an important translational technology that has significantly accelerated the clinical introduction of mRNA platforms. We have developed an mRNA platform that provides long-term expression after both intramuscular and intravenous application. The platform has been extensively characterized using firefly luciferase (Fluc) as a reporter. An intramuscular administration of LNP-mRNA encoding VHH-Fc antibody made it possible to achieve its rapid expression in mice and resulted in 100% protection when challenged with up to 100 LD50 of BoNT/A. The presented approach for the delivery of sdAbs using mRNA technology greatly simplifies drug development for antibody therapy and can be used for emergency prophylaxis.
- Добавил в систему: Дмитриев Сергей Евгеньевич