The prenatal test UNITY, which uses maternal blood samples, is effective in screening for sickle cell disease (SCD), cystic fibrosis (CF), spinal muscular atrophy (SMA), and thalassemias, a study has found.
UNITY is the only prenatal screen test currently available in the market that is able to screen cell-free fetal DNA for genetic mutations associated with SCD, CF, SMA, and different types of thalassemias using one tube of blood from the mother as source material, says the test’s developer, BillionToOne.
The test is currently available in a handful of selected clinics in the U.S., as well as in certain European countries, including Germany, Austria, and the Netherlands.
UNITY is based on BillionToOne’s patent-pending Quantitative Counting Template (QCT) molecular counting technology, which allows researchers to count the number of molecules with a single base-pair resolution.
In practice, because QCT can help identify changes in individual building blocks of a DNA sequence, it can be used as a basis for single-gene non-invasive prenatal tests (sgNIPTs) for a series of genetic disorders, as well as to detect rare genetic variants in liquid biopsies.
In the study, investigators from BillionToOne showed that QCT can accurately determine the number of DNA molecules produced during a polymerase chain reaction (PCR), which is a technique that uses short genetic sequences acting as guiding templates (primers) to produce a large number of DNA molecules containing a specific region of interest.
When researchers used QCT as the basis to develop sgNIPTS for SCD, CF, SMA, and alpha and beta thalassemia and tested its effectiveness on up to 1,000 artificially-generated samples, they found that sgNIPTS had a sensitivity of more than 98% and a specificity of more than 99%.
These QCT-based sgNIPTs were also validated in blood samples that had been collected from 208 healthy pregnant women, including three who carried a mutation in the HBB gene which is associated with beta thalassemia. In all cases, the results from the prenatal tests were consistent with newborn follow-up screening tests.
“BillionToOne’s molecular counter improves the resolution of cell-free DNA testing over a 1,000-fold compared to traditional NIPT methods,” Oguzhan Atay, CEO and co-founder of BillionToOne, said in a news release. “We are excited to publish our detailed methodology and results that showcase accurate single-gene NIPT calls that underlie UNITY.”
The American College of Obstetricians and Gynecologists recommends all pregnant women be screened to determine if they are carriers of mutations associated with CF, SMA, SCD, and thalassemia.
In cases where the mother is found to be a carrier of any of these mutations, it is advisable to re-analyze their blood to determine the risks of their unborn baby developing any of these disorders. UNITY is the first prenatal screen test that allows this type of risk estimation, without requiring the father’s DNA to be tested.
“QCT molecular counting platform has the potential to serve a wide range of unmet clinical needs from single-gene NIPT to copy number variations in liquid biopsies,” said Dr. David Tsao, chief technology officer and co-founder of BillionToOne, and the first author of the study. “With UNITY, we are able to screen for most common genetic disorders directly in the baby from maternal blood alone.”
Compared to traditional screening methods, UNITY is faster, more affordable, and less burdensome for technicians and clinicians — taking between five to 10 days, while conventional carrier screening processes may take up to 12 weeks to complete.
BillionToOne is also working on making UNITY billable through existing insurance codes for standard carrier testing, which are reimbursable by most U.S. insurance providers, including Medicaid.
Of note, some of the researchers have links to the company, which also funded part of the study.