A Next-Generation Approach to Prenatal Testing

The future of non-invasive prenatal testing (NIPT) is around the corner, according to startup Natera (San Carlos, CA).

The future of non-invasive prenatal testing (NIPT) is around the corner, according to startup Natera (San Carlos, CA). The company plans on launching a test later this year that can detect multiple genetic disorders: trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome), trisomy 13 (Patau syndrome), in addition to a number of sex chromosome abnormalities.

The first generation of NIPT technology, which makes use of DNA sequencing technology to safely and reliably detect conditions such as Down syndrome, is based on a on a counting technology, explains Gautam Kollu, vice president of marketing and business development for Natera. “In this approach, you are trying to see how many copies of the chromosome in question exist in the sample from the mother’s bloodstream—typically it is chromosome 21,” he explains. “If that is higher than what you would expect given the amount of fetal DNA matter in the bloodstream, then you know that it is resulting from a trisomy.”

Natera is developing a next-generation non-invasive prenatal test with the ability to highly accurately detect multiple chromosomal abnormalities, including sex chromosomes.

“Our technology uses a very informatics based approach,” Kollu says. “What enables us to do that is that we have picked out single nucleotide polymorphisms, which exist in every individual, but we picked out the ones that are the most informative and we are using 10,000s of them, in combination with information from the Human Genome Project, to be able to generate many hypotheses of the fetal DNA sequence. These hypotheses are compared to the actual fetal DNA sequence to give a highly accurate read of what is happening on chromosomes 13, 18, 21, x and y,” he adds.

The first-generation of NIPT works well in detecting trisomy 21, Kollu explains, “because chromosome 21 is reliably amplified, especially when you compare it to a reference chromosome like chromosome 1. But when you start getting to other chromosomes, like chromosome 13 or the sex chromosomes: x and y, that begins to fall apart, because those chromosomes have a different amount of guanine-cytosine content.”


“Our technology uses a very informatics based approach.”

—Gautam Kollu, VP, marketing and business development

Of the chromosomal abnormalities, Down syndrome gets the most attention and is the most common, affecting between one in 500 to one in 800 pregnancies. “When you start to add in all of the other trisomies as well as the sex chromosome abnormalities, then the numbers are in the one in 200 range per pregnancies,” Kollu says.

Looking to the Future

In a short period of time, NIPTs have become a sizable segment of the prenatal testing space, which was estimated to be worth $1.3 billion in 2010. The market is expected to rapidly grow going forward. “The explosion of new sequencing technology and the fact that it is following a curve that is accelerating than Moore’s law just opens up possibilities very quickly,” says Jonathan Sheena, chief technology officer and co-founder of Natera. “In that sense, it is analogous to the exponential growth you saw in early Internet and tech companies. You just have all of this additional power to work with year on year.”


“We are addressing something that most families go through in the course of their lives.”

—Jonathan Sheena,
founder and CTO

Natera expects that its NIPT will have broader clinical coverage in the future and that the technology will eventually be able to detect subchromosomal abnormalities such as microduplications or microdeletions. At present, those abnormalities can be detected using amniocentesis or chorionic villus sampling but those invasive procedures subject the mother and fetus to risk.

“People have been talking about how sequencing is getting cheaper and more ubiquitous but all of that has been in the context of using sequencing in the context of research applications,” Kollu says. “It is only within the last 12 months or so that people have really started talking about sequencing for clinical applications. The field of NIPT is one example of this but there are not that many others yet. But this field is about to really blossom.”


Matthew Rabinowitz, PhD, CEO 
Jonathan Sheena, CTO
Brad Roberts, COO and VP, finance
Gautam Kollu, VP, marketing and business development
Steve Chapman, VP, sales
Matthew Hill, Ph.D., VP, research
Jennifer Keller, VP, clinical affairs and medical education


San Carlos, CA  | 650/249-9090


 Focus Going Forward

  • Launch of a new non-invasive prenatal test (NIPT) this year.
  • Continue to advance ongoing clinical trials evaluating NIPT in multiple prenatal testing settings.
  • Focus on expanding NIPT to include detection of subchromosomal abnormalities, e.g. microdeletions.


  • July 2012: Launched a genetic carrier screening test.
  • January 2012: Completed a $20 million financing round.
  • August 2011: Launched a non-invasive paternity test. 

The path to market for NIPT products is CMS’s CLIA validation. At some point, however, FDA may get involved in regulating the technology. “The FDA has already said that it wishes to regulate in vitro diagnostic multivariate index assays,” Kollu says. “We are talking to FDA about what is the best way for us to work together. We think having the FDA involved would be a good thing not just for the field but for patients.”

 Brian Buntz is the editor-at-large at UBM Canon's medical group. Follow him on Twitter at @brian_buntz.

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