Researchers at the Indian Institute of Technology Roorkee (IIT Roorkee), with several national collaborators, successfully developed a high-diversity antibody discovery platform. This platform uses shark-derived vNAR antibodies. It is a significant breakthrough that promises to revolutionise the development of diagnostics and therapeutics for numerous conditions, including cancer and infectious diseases. The researchers published the study in the Journal of Biological Chemistry. This work leverages a rare class of antibodies known as Variable New Antigen Receptors (vNARs).
Unique Properties of vNAR Antibodies
Scientists confirm that sharks naturally produce vNAR antibodies, which are significantly smaller and more stable than conventional human antibodies. This compact size offers a major advantage; thus, they can effectively bind to molecular targets inaccessible to larger antibody formats. Moreover, vNARs are exceptionally small, typically weighing only 12 to 15 kDa. Consequently, their size enables better tissue penetration and binding to intricate protein clefts and functional sites. In addition, these single-domain antibodies maintain functionality under extreme conditions, such as high temperatures and low pH. This gives them a notable edge over conventional antibodies.
Universal Antibody Discovery Platform
For the study, the research team created a vast library containing nearly 300 billion distinct vNAR antibody variants. They sourced these single-domain variants from the white-spotted bamboo shark. Since the source shark was naïve (not exposed to specific pathogens), the resulting library functions as a universal antibody discovery system. Consequently, scientists can screen it against an expansive range of disease-related targets. The team demonstrated its efficacy by screening the library against nine different targets. Importantly, these targets included viral proteins, cancer-associated molecules, and snake venom toxins. In every case, the researchers successfully isolated antibodies that showed strong binding properties. Furthermore, the small size of vNARs makes them highly promising for the treatment and early diagnosis of solid tumors, often proving superior to other single-domain antibodies.
Accelerating Affordable Therapeutics in India
This universal, high-diversity antibody discovery system substantially strengthens India’s capacity for faster disease response. Furthermore, it accelerates the development of affordable diagnostics and therapeutics for those with the greatest need. The institute has already filed a patent for this novel technology. Therefore, the researchers collaborated with IMGENEX India Pvt Ltd to explore and develop its diagnostic and therapeutic applications. vNARs have successfully demonstrated utility in other studies as well. They show potential for applications like drug delivery, imaging, and neutralizing infectious agents like SARS-CoV-2.
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Frequently Asked Questions
Q1: What are vNAR antibodies and why are they considered a breakthrough?
vNAR (Variable New Antigen Receptor) antibodies are a rare class of small, single-domain antibodies produced by sharks. They are considered a breakthrough because their compact size (12-15 kDa) and superior stability allow them to bind to molecular targets and hard-to-reach protein clefts that are inaccessible to larger, conventional human antibodies. This makes them ideal for targeted drug delivery and tissue penetration.
Q2: What is the source and diversity of the IIT-R antibody library?
The library was created from the white-spotted bamboo shark. It comprises nearly 300 billion distinct single-domain vNAR antibody variants. Researchers developed it as a universal discovery system, capable of being screened against a wide spectrum of disease-related targets because the source shark had not been exposed to specific pathogens.
Q3: Beyond cancer, what other applications do vNAR antibodies have?
The IIT-R platform and vNAR antibodies in general are being explored for a wide range of biomedical applications. These include diagnostics, therapeutics for infectious diseases (like viral proteins), snake venom toxins, auto-inflammatory conditions, and enhancing drug delivery or imaging due to their superior tissue penetration.
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References
- IIT-R develops shark-based antibody discovery platform for cancer, otherdiseases – ETHealthworld.
- Unleashing the power of shark variable single domains (VNARs): broadly neutralizing tools for combating SARS-CoV-2 – Frontiers.
- Shark New Antigen Receptor (IgNAR): Structure, Characteristics and Potential Biomedical Applications – PMC – NIH.
- Shark IgNAR: The Next Broad Application Antibody in Clinical Diagnoses and Tumor Therapies? – MDPI.
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