RedShiftBio Apollo for automated biomolecular structure, similarity and stability

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Targeted therapy is the foundation of precision medicine today and is driving research efforts particularly for cancer research. Antibody drug conjugates (ADCs) are biotherapeutic proteins gaining widespread use for delivery of chemotherapeutic drugs targeted to cancer cells. Unlike conventional methods, more potent drugs can be delivered using lower dosages while sparing healthy cells and minimising systemic toxicity. Critical to the success is maintaining the native structure of the monoclonal antibody within the conjugate since this underpins the targeting efficiency and stability.

Consequently, the direct link between the structure and functionality of a biotherapeutic protein makes it essential to develop biopharmaceuticals that deliver the molecule with its target structure intact. By their own nature, proteins are prone to conformational change and aggregation in solution which can compromise efficacy and impact safety and thus must be understood and controlled. The development of an optimised formulation therefore relies on being able to sensitively detect changes in secondary and higher-order structure.

While circular dichroism (CD) and Fourier transform infrared (FTIR) spectroscopy are commonly utilised for characterising the secondary structure of proteins, they have recognised limitations. While CD works most effectively at lower concentrations, it is not compatible with many excipients and buffers. Ill-suited to automation and relatively slow, FTIR is manually intensive and lacks the sensitivity required to detect structural changes.

Microfluidic modulation spectroscopy (MMS) is a new technique that should make it easier to exploit the inherent advantages of IR spectroscopy for measurements of secondary structure. It uses a mid-IR light source to probe absorption within the Amide I band (1714 to 1590 cm^-1) associated with C=O stretching in the polypeptide backbone. However, at the heart of an MMS system is a modulating microfluidic flow cell that continuously switches between the sample (protein solution) and reference (buffer) streams, used for automatic real-time background correction of the sample spectra. As a result, measurements should be less impacted by noise and less sensitive to background drift. MMS requires minimal sample preparation and it is automated for unmanned operation. It can be used for a wide range of biomolecules, from mAb-based biotherapeutics to robust measurements of ADCs, AAVs and mRNA.

The RedShiftBio Apollo is a second-generation flagship system featuring MMS technology. For more information or a product demo, visit https://www.atascientific.com.au/products/redshiftbio-apollo/.