For many expectant parents, pregnancy is a time of excitement, yet this time can also be riddled with uncertainty. Unexpected complications affect one in five pregnancies1. Likewise, only one in five pregnancy complications can be predicted by current clinical assessments, many of which are invasive, risky, and fraught with bias. Thus, there is a pressing need for a more comprehensive pathophysiological understanding and more rigorous, yet safe, diagnostic procedures.
Performing a liquid biopsy on almost any bodily fluid can identify a plethora of biomarkers originating from many different parts of the body, and these biomarkers can be mapped back to their site of origin. Cell-free RNA (cfRNA) is one of these biomarkers, and cfRNA originating from the foetus or the placenta can be detected in a sample of the mother’s blood – much safer than performing amniotic testing.
New applications – combining RNA-seq and AI
At the start of 2022, research published in Nature revealed that health technology platform Mirvie’s combination of machine-learning with single-cell RNA-seq analysis of foetal and maternal cfRNA can accurately identify 75% of women who later develop pre-eclampsia; a condition associated with maternal endothelial dysfunction and high blood pressure affecting up to 1 in 12 pregnancies1. Pre-eclampsia is largely responsible for maternal morbidity, and symptoms often don’t manifest until the third trimester. What’s particularly promising about Mirvie’s technology is that diagnosis could be carried out at a much earlier stage in the second trimester, opening up new therapeutic windows for improving clinical outcomes for mother and baby.
By identifying gene sets that experience temporal changes in expression during pregnancy and foetal development, this technique additionally helped monitor pregnancy progression, independent of clinical factors. Encouragingly, this study was conducted on a large and diverse cohort (in terms of race, age, ethnicity, health status, BMI), and the results indicate that such factors have a negligible impact on the evaluation of results, unlike current, state-of-the-art methods.
Populating the field
piRNA (a type of short non-coding RNA) in maternal plasma-derived exosomes can also be detected in a blood sample for the early diagnosis of foetal congenital defects that cannot be seen during early prenatal ultrasound screening2. Another prenatal screening platform by Natera evaluates single nucleotide polymorphisms in foetal cfDNA to indicate the risk of common genetic conditions that are caused by extra or missing chromosomes3. Evidently, analysis of cfDNA and RNA really has the potential to revolutionise what we understand about the developing foetus and prenatal conditions.
This area of precision therapeutics is a booming field with endless applications. We’ve already reported on the broad application of liquid biopsy technology - from cancer to concussion – and interest from a commercial standpoint is accelerating:
- A Research and Markets report of June 2021 reported the existence of almost 2500 patent families concerning cfDNA/RNA4.
- Includes filings by Roche and Illumina.
- Growing number of EP oppositions and US litigations for patent infringement.
- Mirvie have raised more $30 million in early-stage financing since 2018, and at roughly $10 per test, this platform has the potential to be extremely accessible.
- The FDA has granted 3 Breakthrough Device Designations for the Natera test.
Researchers and investors alike are beginning to see the need and opportunity that surrounds the drive towards advancing our understanding of women’s health, and precision diagnostics is a promising vehicle for this campaign.
- Rasmussen, M., Reddy, M., Nolan, R. et al.RNA profiles reveal signatures of future health and disease in pregnancy. Nature 601, 422–427 (2022). https://doi.org/10.1038/s41586-021-04249-w
- Jia, S., Zhang, Q., Wang, Y. et al. PIWI-interacting RNA sequencing profiles in maternal plasma-derived exosomes reveal novel non-invasive prenatal biomarkers for the early diagnosis of nonsyndromic cleft lip and palate. eBioMedicine 65, 103253 (2021). https://doi.org/10.1016/j.ebiom.2021.103253
- Dar, P., Jacobson, B., Clifton, R., et al. Cell-free DNA screening for prenatal detection of 22q11.2 deletion syndrome. American Journal of Obstetrics and Gynecology (2022). https://doi.org/10.1016/j.ajog.2022.01.002
- Circulating DNA/RNA Patent Landscape 2021. Research and Markets, 5354129 (2021) https://www.researchandmarkets.com/reports/5354129/circulating-dnarna-patent-landscape-2021
Alice Jefferies and Fran Salisbury also discussed this topic in Life Sciences Intellectual Property Review.
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