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Circulating RNA signatures specific to preeclampsia

A pre-eclampsia, C-RNA technology, applied in the field of circulating RNA identification specific to pre-eclampsia, can solve the problem of lack of discrimination and prediction ability of patients, etc.

Pending Publication Date: 2020-02-11
ILLUMINA INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although various protein biomarkers show variable levels in maternal serum during the presymptomatic phase, these biomarkers lack discriminative and predictive power for individual patients (Karumanchi and Granger, 2016, Hypertension [hypertension]; 67(2 ):238-242)

Method used

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  • Circulating RNA signatures specific to preeclampsia
  • Circulating RNA signatures specific to preeclampsia
  • Circulating RNA signatures specific to preeclampsia

Examples

Experimental program
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Effect test

example 1

[0204] Pregnancy-specific C-RNA markers

[0205] The presence of circulating nucleic acids in maternal plasma provides a window into fetal and placental progression and health ( figure 1 ). Circulating RNA (C-RNA) is detected in the maternal circulation and originates from two main sources. A large fraction of C-RNA originates from apoptotic cells that release C-RNA-containing vesicles into the bloodstream. C-RNA also enters the maternal circulation through the shedding of active signaling vesicles (eg, exosomes and microvesicles) from various cell types. Such as figure 2 As shown, C-RNA thus consists of by-products of cell death as well as active signaling products. Characteristics of C-RNA include being produced by common processes, being released from cells throughout the body, and being stable and contained in vesicles. It represents the circulating transcriptome, which reflects tissue-specific changes in gene expression, signaling, and cell death.

[0206] C-RNA ma...

example 2

[0212] C-RNA labeling across gestational ages

[0213] This example characterizes C-RNA signatures across different gestational ages throughout pregnancy. It is expected that the changes in C-RNA signatures at different time points throughout pregnancy will be more subtle than the differences noted in Example 1 between C-RNA signatures of pregnant and non-pregnant samples. Such as Figure 5 As shown, as the pregnancy progressed, the C-RNA profile of the marker genes was observed to change significantly over time, with a clear set of genes upregulated in the early period and a clear set of genes increased in the late period.

[0214] These genes include CGB8, CGB5, ZSCAN23, HSPA1A, PMAIP1, C8orf4, ITM2B, IFIT2, CD74, HSPA6, TFAP2A, TRPV6, EXPH5, ​​CAPN6, ALDH3B2, RAB3B, MUC15, GSTA3, GRHL2, and CSHL1, as Figure 5 listed.

[0215] These genes may also include CSHL1, CSH2, KISS1, CGA, PLAC4, PSG1, GH2, PSG3, PSG4, PSG7, PSG11, CSH1, PSG2, HSD3B1, GRHL2, LGALS14, FCGR1C, PSG5,...

example 3

[0218] C-RNA signature of preeclampsia

[0219] In the case of this example, a C-RNA signature unique to preeclampsia was identified. Will be diagnosed with aura in two studies (the RGH14 study (registered with clinical trials.gov as NCT0208494) and the Pearl study (also referred to herein as the Pearl Biobank; registered with clinical trials.gov as NCT02379832)) C-RNA identification was determined in the collected samples of pregnant women with eclampsia and analyzed ( Figure 6 ). Two tubes of blood were collected at the time of diagnosis of preeclampsia. Eighty gestational age-matched control samples were collected to minimize transcriptional variability independent of preeclamptic disease status and to control for gestational age differences in C-RNA signatures. Samples from the RGH14 study were used to identify a panel of biologically relevant genes, and the predictive value of these biomarkers was validated in an independent cohort of samples from the Pearl Biobank. ...

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Abstract

The present invention includes methods and materials for use in the detection preeclampsia and / or determining an increased risk for preeclampsia in a pregnant female, the method including identifyingin a biosample obtained from the pregnant women a plurality of circulating RNA (C-RNA) molecules.

Description

[0001] Continue to apply for data [0002] This application claims the benefit of U.S. Provisional Application Serial No. 62 / 676,436, filed May 25, 2018, and U.S. Provisional Application Serial No. 62 / 848,219, filed May 15, 2019, each of which is incorporated herein by reference in its entirety . technical field [0003] The present invention generally relates to methods and materials for the detection and early risk assessment of the pregnancy complication preeclampsia. Background technique [0004] Preeclampsia is a condition that occurs only during pregnancy, affecting 5% to 8% of all pregnancies. It is the direct cause of 10%-15% of maternal deaths and 40% of fetal deaths. The three main symptoms of preeclampsia can include high blood pressure after the 20th week of pregnancy, swelling in the hands and feet, and excess protein in the urine (proteinuria). Other signs and symptoms of preeclampsia may include severe headache, vision changes (including temporary vision lo...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6883
CPCC12Q1/6883C12Q2600/156C12Q2600/158G01N33/5308G01N2800/368G01N2800/50
Inventor S·E·蒙切尔F·卡佩尔S·金宁斯S·罗尔贝克C·兰迪斯-辛奇里夫
Owner ILLUMINA INC
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