Circular Genomics Joins Lilly Gateway Labs in San Diego!
Unlocking the Potential of Circular RNA
SCIENCE
What is circular RNA?
These molecules are particularly abundant in the brain, exhibit remarkable stability compared to linear RNAs, and are believed to possess important biological functions due to being conserved across different species.
Circular RNAs are a unique class of non-coding RNAs generated through backsplicing of precursor mRNAs during processing.
Circular RNAs have been shown to be important for brain development, maturation, function, and aging and have been linked to many psychiatric and neurological disorders, including major depressive disorder (MDD) and Alzheimer's disease.
Their abnormal expression in pathological states positions them as novel diagnostic and predictive biomarkers for numerous brain disorders.⁴
1,2,3
Circular RNAs are highly sensitive to changes in neuronal activity or activation of various neuronal receptors and cross the blood-brain barrier. They are highly stable so are readily detectable in the blood.
At Circular Genomics, we lead the way in utilizing circular RNA biomarkers, valued for their enhanced stability, to develop diagnostic and therapeutic response tests.
Unlike DNA pharmacogenetic testing, which reports the static disposition of genetic inheritance to metabolize a drug, circular RNAs reflect an individual's current biological state, providing real-time insights on their likelihood to respond to a given treatment. This dynamic quality of circular RNAs, and their capacity to directly predict response to treatment makes them invaluable for precision psychiatry. Our innovative tests aim to transform the standard of care, offering critical insights for diagnosing, monitoring, and treating psychiatric and neurological conditions.
Key highlights
Identification and validation of circular RNA biomarker
5,6
Among MDD patients, we observed close to 90% higher baseline (before treatment) blood levels of circular RNA biomarker (circRNAx) in patients who did not respond to sertraline (SERT NR) compared to those who did respond (SERT R). n=110 patients, p-value < 0.0001.*
Dynamic biomarker response to treatment
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Significant increases in circular RNA biomarker levels were seen after 8 weeks of sertraline treatment in responders to sertraline (SERT R). This observation indicates that this circular RNA biomarker is responsive to treatment, and displays a dynamic expression profile longitudinally.
Linkage to known mechanisms of antidepressant response
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Levels of circRNAx are correlated with activation of serotonin and brain-derived neurotrophic factor (BDNF), which modulate response to SSRI.
Performance Data
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Data from our EMBARC and ANTARES studies showed that MindLight had an overall diagnostic accuracy of 77% for predicting response to SSRI treatment in patients with MDD. (PPV=77%, NPV=77%, 1-NPV=23%, ratio between "High Likelihood" and "Low Likelihood" patient response rates = 3.4x. n=101)*
*Response is defined as a 50% or more reduction in HAMD-17 symptom severity following 8 weeks of treatment.
Our pipeline of circular RNA biomarker programs
Our circular RNA biomarker programs are meeting a crucial market demand for evidence-based psychiatric and neurological healthcare. We have several programs in the pipeline that are well positioned for precision psychiatry needs.
Related publications
May 1, 2024
A brain-enriched circRNA blood biomarker can predict response to SSRI antidepressants
Major Depressive Disorder (MDD) is a debilitating psychiatric disorder that currently affects more than 20% of the adult US population and is a leading cause of disability worldwide. Although treatment with antidepressants, such as Selective Serotonin Reuptake Inhibitors (SSRIs)…
February 17, 2023
Prenatal alcohol exposure results in brain region- and sex-specific changes in circHomer1 expression in adult mouse brain
Circular RNAs (circRNAs) are a novel category of covalently-closed non-coding RNAs mainly derived from the back-splicing of exons or introns of protein-coding genes. In addition to their inherent high overall stability, circRNAs, have been shown to have strong functional effects on gene expression via a multitude of transcriptional and post-transcriptional mechanisms...
August 4, 2022
Knockdown of circHomer1 in the orbitofrontal cortex results in differential encoding of salient stimuli
CircHomer1 is an activity-dependent circular RNA (circRNA) isoform produced from back-splicing of the Homer1 transcript. Homer1 isoforms are well-known regulators of homeostatic synaptic plasticity through post-synaptic density scaffold regulation. Homer1 polymorphisms have been associated with psychiatric diseases including schizophrenia (SCZ) and…
1. Song, R. et al. Plasma Circular RNA DYM Related to Major Depressive Disorder and Rapid Antidepressant Effect Treated by Visual Cortical Repetitive Transcranial Magnetic Stimulation. J. Affect. Disord. 274, 486–493 (2020).
2. Zimmerman, A. J. et al. A psychiatric disease-related circular RNA controls synaptic gene expression and cognition. Mol. Psychiatry 25, 2712–2727 (2020).
3. Dube, U. et al. An atlas of cortical circular RNA expression in Alzheimer disease brains demonstrates clinical and pathological associations. Nat. Neurosci. 22, 1903–1912 (2019).
4. Verduci, L., Tarcitano, E., Strano, S., Yarden, Y. & Blandino, G. CircRNAs: role in human diseases and potential use as biomarkers. Cell Death Dis. 12, 468 (2021).
5. Papageorgiou G, Ibrahim EC, Maxson G, et al. A brain-enriched circRNA blood biomarker can predict response to SSRI antidepressants. bioRxiv.org. https://www.biorxiv.org/content/10.1101/2024.04.30.591973v1. Published May 1, 2024.
6. Data on file, publication pending
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