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Current advancements in B-cell receptor sequencing fast-track the development of synthetic antibodies

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Abstract

Synthetic antibodies (Abs) are a class of engineered proteins designed to mimic the functions of natural Abs. These are produced entirely in vitro, eliminating the need for an immune response. As such, synthetic Abs have transformed the traditional methods of raising Abs. Likewise, deep sequencing technologies have revolutionized genomics and molecular biology. These enable the rapid and cost-effective sequencing of DNA and RNA molecules. They have allowed for accurate and inexpensive analysis of entire genomes and transcriptomes. Notably, via deep sequencing it is now possible to sequence a person’s entire B-cell receptor immune repertoire, termed BCR sequencing. This procedure allows for big data explorations of natural Abs associated with an immune response. Importantly, the identified sequences have the ability to improve the design and engineering of synthetic Abs by offering an initial sequence framework for downstream optimizations. Additionally, machine learning algorithms can be introduced to leverage the vast amount of BCR sequencing datasets to rapidly identify patterns hidden in big data to effectively make in silico predictions of antigen selective synthetic Abs. Thus, the convergence of BCR sequencing, machine learning, and synthetic Ab development has effectively promoted a new era in Ab therapeutics. The combination of these technologies is driving rapid advances in precision medicine, diagnostics, and personalized treatments.

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Abbreviations

Abs:

Antibodies

mAbs:

Monoclonal Abs

NGS:

Next-generation sequencing

BCRs:

B-cell receptors

Ig:

Immunoglobulins

CDRs:

Complementary determining regions

V:

Variable

J:

Joining

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Acknowledgements

The author would like to thank Peter Olson and Janet Stewart for reviewing of this article and providing detailed suggestions.

Funding

This work was partially supported by RevivAb Educational Advancement Grant MT-021.

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  1. Avance Biologicals, Department of Medicinal Chemistry, 950 Dupont Street, Toronto, ON, M6H 1Z2, Canada

    Eugenio Gallo

  2. RevivAb, Department of Protein Engineering, Av. Ipiranga, 6681, Partenon, Porto Alegre, RS, 90619-900, Brazil

    Eugenio Gallo

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EG made substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data; or the creation of new software used in the work; EG drafted the work or revised it critically for important intellectual content; EG approved the version to be published; and EG agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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Gallo, E. Current advancements in B-cell receptor sequencing fast-track the development of synthetic antibodies. Mol Biol Rep 51, 134 (2024). https://doi.org/10.1007/s11033-023-08941-0

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