Highly multiplexed proteomic platform for biomarker discovery, diagnostics, and therapeutics

Area of Science:

• Biochemistry
• Molecular Biology
• Proteomics

Background:

• Disease progression involves complex proteomic changes.
• Proteins provide real-time health status, unlike genomic predictions.
• Current proteomics methods face limitations in scale and efficiency.

Purpose of the Study:

• To introduce a new aptamer-based proteomics technology for large-scale biomarker discovery.
• To enable simultaneous measurement of over a thousand proteins from small biological samples.
• To apply this technology for identifying protein expression changes in diseases like CKD and NSCLC.

Main Methods:

• Development of Slow Off-rate Modified Aptamers (SOMAmers) with chemically modified nucleotides.
• Utilizing SOMAmers' dual nature for protein-to-DNA signature transformation.
• Quantification of DNA signatures on commercial DNA microarray platforms.

Main Results:

• Simultaneous measurement of 1,030 proteins with sub-pM detection limits.
• Assay exhibits a dynamic range of >3 logs for individual analytes and 7 logs overall.
• High throughput capability of one million analytes per week.

Conclusions:

• The new proteomics technology is fast, economical, scalable, and flexible.
• Enables whole-proteome analysis and biomarker discovery for personalized diagnostics and therapeutics.
• Demonstrated application in identifying biomarkers for chronic kidney disease and non-small cell lung cancer.