PharmaShots: “Shedding Light on Sapient’s Recently Launched Discovery Proteomics Services”

Proteomics has become a hot area of interest and is of growing importance to biopharma for good reason. Proteins orchestrate many biological functions, and changes in the proteome occurring over time can be reflective of biological dysfunction, disease processes, or drug response. Understanding these dynamic changes is absolutely essential as part of the drug development process. There is an abundance of scientific literature to suggest that instituting a drug development program together with biomarkers greatly increases overall approval rates, irrespective of drug modality and therapeutic area. Discovery of protein biomarkers that can be used for disease diagnostics, companion diagnostics, and as target engagement and pharmacodynamic markers can complement genomics data and drive new insights needed to advance precision drug development. 

Saurabh: Tell us how your high throughput proteomics services will contribute to the discovery of dynamic biomarkers. 

Mo: Sapient’s discovery proteomics offering will help the scientific community more quickly realize the ability to identify and leverage circulating protein biomarkers for key applications such as early disease detection, patient stratification in clinical trials, disease prognosis, and ultimately, for guiding implementation of precision-based therapeutics. These biomarkers can play a critical role in aligning individuals with a specific disease subtype with an optimal therapy, as well as for evaluating the efficacy of that drug at a very early timepoint as markers of target engagement and pharmacodynamic response. 

To enable greater discovery in plasma proteomics, we had to address a significant bioanalytical hurdle: the vast dynamic range of proteins in blood, which spans 10 to 12 orders of magnitude. Current state-of-the-art methods rely on binding agents like antibodies or aptamers to selectively isolate proteins of interest, followed by readout via genetic sequencing or gene chip technology. However, these methods present challenges, including imperfect binding fidelity and an inability to capture dynamic changes in protein structures. Protein variants and post-translational modifications (PTMs) serve as crucial on/off switches for protein functions and are where much of the biologically important information is encoded. 

Our discovery proteomics methods embrace mass spectrometry as a transformative technology, capable of directly mapping and sequencing peptide fragments that are part of a protein to achieve accurate protein identification. We’ve innovated our technologies and approaches to address the inherent limitations of mass spectrometry-based proteomics, firstly by utilizing nanoparticles for protein extraction from blood to overcome the issue of dynamic range. Of importance, our nanoparticle enrichment captures plasma proteins as well as exosomal and membrane-bound proteins which may be key for early detection. Secondly, we’ve optimized our systems for high throughput to allow for analysis of these extracted proteins and PTMs with greater speed. 

Today, we can measure thousands of proteins in thousands of samples with high fidelity, using peptide mapping with interrogation of PTMs including phosphorylation, acetylation, methylation, and ubiquitination. Our approaches enable deep coverage and are optimized for revealing biological insights from the blood and tissue proteome.