A DNA sequence used in thousands of medical diagnostic tests doesn't actually bind to the protein it is supposed to detect.
April 25, 2026
Original Paper
A Widely Used CRP Aptamer Does Not Bind CRP, Revealing a General Route to Surface-Driven Pseudoaffinity in Biosensors
SSRN · 6643242
The Takeaway
C-reactive protein is a major marker for inflammation, and many biosensors rely on a specific DNA strand called an aptamer to find it. This study reveals that this widely used aptamer has no actual affinity for the protein when it is floating in a solution. The positive results seen in previous experiments were likely caused by the sensor surface properties rather than real biological recognition. This pseudoaffinity means that many medical results and research papers may be based on a fundamental technical error. Scientists now have to re-evaluate these diagnostic tools to ensure they are actually measuring what they claim to measure. It exposes a ghost in the machinery of medical diagnostics.
From the abstract
Aptamer sequences are often reused in biosensors and diagnostics without independent confirmation of binding activity, even though rigorous validation requires quantitative solution-phase testing by orthogonal methods. Here, we re-examined a DNA sequence reported in 2010 to bind C-reactive protein (CRP) with a Kd of 3.5 nM by surface plasmon resonance (SPR) and subsequently adopted in many CRP aptasensors. We tested this sequence by two orthogonal solution-phase methods and SPR. In solution-phas