# A Platform for Safe, Noninvasive Prenatal Genetic Testing at Five Weeks of Pregnancy

> **NIH NIH R44** · CRADLE GENOMICS, INC. · 2020 · $901,625

## Abstract

The purpose of this research is to provide a flexible prenatal genetic testing product that can be expanded to
detect any inheritable trait as early as 5, and up to 20, weeks of gestation, from a safe, noninvasive Pap smear.
Published studies, as well as our own experience, show that perinatal Pap collections using a cervical cytobrush
pose no risk to mother or fetus, and captures trophoblast cells that migrate from the placenta into the reproductive
tract. Trophoblast retrieval and isolation from the cervix (TRIC) efficiently isolates hundreds of trophoblast cells
without limitations due to early gestational age, maternal obesity, or uteroplacental insufficiency disorders. In our
report published in Science Translational Medicine, we isolated sufficient genomic DNA from intact fetal
trophoblast cells obtained by TRIC at 5-19 weeks of gestation (n=20) to definitively distinguish maternal and fetal
DNA by targeted next-generation sequencing (NGS) of short terminal repeats (STRs) and single nucleotide
polymorphisms (SNPs). Compared to massively parallel sequencing of cell-free fetal DNA from maternal serum,
which has a fetal fraction of only 4-10% at week 10 of gestation, the complete genome obtained by TRIC has a
fetal fraction of 85-100%, and provides nucleotide-specific haplotyping. In our Phase I award, we developed this
technology for prenatal genotyping of single gene disorders located on the hemoglobin B (HBB) gene, using
custom multiplex PCR amplification of SNPs, STRs and loci across HBB for NGS. We successfully haplotyped
the locus for the sickle cell disease (SCD) point mutation and genotyped the remainder of the HBB exome, which
includes alternate SCD loci, beta thalassemias and anemias. In Phase II, we will expand the test to include HBA1
and HBA1 genes (alpha thalassemias) to provide a comprehensive hemoglobinopathy screen. Phase I studies
revealed that genotyping was consistently accurate, unless cervical specimen collection was suboptimal and
<40 trophoblast cells were isolated. Commercialization will require operators to obtain adequate specimens. We
will accomplish six milestones towards commercialization of this test: 1. Incorporate the HBA1 and HBA2 loci
into a comprehensive hemoglobinopathy test. 2. Optimize success rates through operator training and
innovations in collection device designs to increase cervical cell recoveries. 3. Innovate a novel alternative
method to cytobrush-based cervical collection. 4. Automate the TRIC processing pipeline for high throughput
cell isolation, DNA purification and NGS. 5. Establish sample quality assessment tools powered by artificial
intelligence and machine learning. 6. Perform a clinical validation trial to assess test performance. With an
estimated annual market potential over $284 million for prenatal hemoglobinopathies testing, the envisioned
technology will fill an existing gap in clinical diagnostics and outcompete existing invasive prenatal testing. Our
initial commercial product ...

## Key facts

- **NIH application ID:** 9940863
- **Project number:** 5R44HD092205-03
- **Recipient organization:** CRADLE GENOMICS, INC.
- **Principal Investigator:** David Randall Armant
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $901,625
- **Award type:** 5
- **Project period:** 2017-07-19 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9940863

## Citation

> US National Institutes of Health, RePORTER application 9940863, A Platform for Safe, Noninvasive Prenatal Genetic Testing at Five Weeks of Pregnancy (5R44HD092205-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9940863. Licensed CC0.

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