March 23, 2021

Yuning Wang, PhD*,1, Jennifer Crha, MSc#,1, Jessica Barber, MPH#,1
*Author
#Reviewer
1Rapid Novor, Inc.

Abstract

Antibodies are integral to life sciences research and therapeutic and diagnostics discovery and development. However, they are inherently prone to variability. Even when expressed as monoclonal antibodies, cell culture systems may harbor mistakes that produce a different antibody, leading to batch-to-batch variability, and experimental irreproducibility. The term reproducibility crisis is a term coined in the early 2010s to denote the lack of consistency observed in research results, particularly as it pertained to immunoreagents. To solve this crisis, researchers have proposed robust protocols, and number identifiers to catalogue and track antibodies through publications to ensure reproducibility. However, these identifiers do not include the protein sequence as an important property that requires certification. In this review, we discuss why this paucity in protein sequence verification substantially contributes to antibody irreproducibility.

Key Takeaways

  • Antibodies are a staple tool in the life sciences; with their use, researchers continue to afford discoveries that would otherwise be much more difficult to realize
  • Antibody spending costs upwards of $3 billion in the US alone, and about half of this sum is accounted to irreproducible research
  • Antibodies require extensive validation; however, among the type of validation required, verification of protein sequences is not yet emphasized by the field despite its importance
  • With de novo protein sequencing, scientists can ensure that the final product’s sequence has not changed from batch to batch
  • De novo protein sequencing is a great tool to derive the amino acid code of an antibody in its entirety, and access additional insights into its structure that are critical to its characterization for therapeutic development

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Content

  1. Antibodies and the Reproducibility Crisis
  2. Top 3 Causes of the Antibody Reproducibility Crisis
  3. The Economic Impact of Antibody Irreproducibility
  4. Moving Towards Recombinant Antibodies
  5. Tackling Irreproducibility with Protein Sequencing
  6. Case Study: Reviving Therapeutic Antibodies
  7. Conclusions

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We Have Sequenced 3000+ Antibodies and We Are Eager to Help You.

Through next generation protein sequencing, Rapid Novor enables reliable discovery and development of novel reagents, diagnostics, and therapeutics. Thanks to our Next Generation Protein Sequencing and antibody discovery services, researchers have furthered thousands of projects, patented antibody therapeutics, and developed the first recombinant polyclonal antibody diagnostics.

Talk to Our Scientists.

We Have Sequenced 3000+ Antibodies and We Are Eager to Help You.

Through next generation protein sequencing, Rapid Novor enables timely and reliable discovery and development of novel reagents, diagnostics, and therapeutics. Thanks to our Next Generation Protein Sequencing and antibody discovery services, researchers have furthered thousands of projects, patented antibody therapeutics, and ran the first recombinant polyclonal antibody diagnostics

Talk to our scientists. We have sequenced over 3000 antibodies and we are eager to help you.