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A review of plant-based expression systems as a platform for single-domain recombinant antibody production

Journal

INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
Volume 193, Issue -, Pages 1130-1137

Publisher

ELSEVIER
DOI: 10.1016/j.ijbiomac.2021.10.126

Keywords

Single-domain antibody; Plant-based expression systems; VHH-Fc

Funding

  1. Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
  2. Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
  3. Fundacao de Amparoa Pesquisa do Estado de Rondonia (FAPERO)
  4. Fundacao Oswaldo Cruz/Fiotec

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VHHs are small functional immunoglobulins that exhibit high tissue penetration and low immunogenicity. They provide superior antigen recognition compared to human antibodies, along with better solubility and stability. Plant-based expression systems offer versatility, cost-effectiveness, safety, and efficiency in producing VHH-related constructs.
Monoclonal antibodies have contributed to improving the treatment of several diseases. However, limitations related to pharmacokinetic parameters and production costs have instigated the search for alternative products. Camelids produce functional immunoglobulins G devoid of light chains and CH1 domains, in which the antigenic recognition site is formed by a single domain called VHH or nanobody. VHHs' small size and similarity to the human VH domain contribute to high tissue penetration and low immunogenicity. In addition, VHHs provide superior antigen recognition compared to human antibodies, better solubility and stability. Due to these characteristics and the possibility of obtaining gene-encoding VHHs, applications of this biological tool, whether as a monomer or in related recombinant constructs, have been reported. To ensure antibody efficacy and costeffectiveness, strategies for their expression, either using prokaryotic or eukaryotic systems, have been utilized. Plant-based expression systems are useful for VHH related constructs that require post-translational modifications. This system has exhibited versatility, low-cost upstream production, and safety. This article presents the main advances associated to the heterologous expression of VHHs in plant systems. Besides, we show insights related to the use of VHHs as a strategy for plant pathogen control and a tool for genomic manipulation in plant systems.

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