SOMAmers: Proteomics to lung cancer to a Wellness Chip
Larry Gold
University of Colorado at Boulder and SomaLogic, Inc.
We figured out a way to make novel aptamers, called SOMAmers. The SOMAmers, made of modified
single-stranded DNA, have high affinities for their target human proteins, and in addition have very
slow off-rates. The high binding quality of these special aptamers is supported by a crystal
structure of one such SOMAmer with its protein partner.
We also figured out a way to use the SOMAmers to do deep proteomics. Today we
measure 1,100 human proteins in serum, plasma, or tissue extracts, using only 15 µl of
sample. The measurements are accurate (CVs of ~ 5%) and very sensitive; more than half the proteins
are measured with limits of detection below pM. The combination of reagents and a novel assay
has made biomarker discovery relatively easy. And thats what we do ...
We get samples from healthy and sick people and do an unbiased experiment by asking if
any proteins on the menu go up or down in the blood of sick people. We
have found many blood biomarkers for lung cancer, mesothelioma, pancreatic cancer, and more.
Lung cancer is the leading cause of cancer deaths. Most cases are diagnosed at an advanced
stage. Patients diagnosed at an early stage who have surgery experience an 86% overall 5-year
survival thus one needs earlier detection of lung cancer.
I will share data from a large clinical trial (almost 1,400 subjects) from four independent
studies of long-term tobacco-exposed populations. We identified 44 candidate biomarkers, from which a 12-
protein panel was constructed. The panel identified NSCLC from controls with 91% sensitivity and 84% specificity
in the training set, and 89% sensitivity and 83% specificity in the blinded, independent verification set.
Performance was similar for early and late stage disease.
We also have compared protein concentrations in NSCLC biopsy materials with literature values for mRNA concentrations
in similar biopsies. The correlations between proteins and their mRNAs are poor, suggesting that a discovery
proteomics platform might be essential for understanding NSCLC biology.
Finally, with only some trepidation, I will describe our goal of transforming medicine through a Wellness
Chip, aimed at the most devastating diseases for which early diagnosis and action could be life-saving.