NGS-ArrayIt, a joint venture between Neo Gen Screening of Bridgeville, Pa. and TeleChem/ Arrayit.com, of Sunnyvale, Calif., has recently inked contracts to use microarrays to screen over a million newborn babies per year for genetic hearing loss disorders.
At the beginning of July, NGS-Arrayit finalized a deal with Oz Systems, a Dallas-based company that delivers neonatal genetic screening services, to implement its microarray screens to detect 15 hearing loss-related genetic mutations in the one million babies that Oz already screens yearly.
This Oz Systems deal followed a June contract with the state of New Jersey to perform this battery of microarray-based tests on all babies born in the state. NGS-Arrayit has a similar ongoing contract with the state of Pennsylvania.
These contracts are what NGS-Arrayit hopes is just the beginning of a $36 million effort to move its microarray technology into the neonatal screening market, said Paul Haje, director of business development for the privately-owned Telechem/Arrayit.com.
The joint venture, which is 67 percent owned by Telechem/Arrayit.com and 33 percent owned by Neo Gen Screening, one of the largest privately owned neonatal screening labs in the US, is combining Telechem/Arrayit.com’s substantial capital with Neo Gen’s “football-sized clinical lab” and robotics, Haje said. The companies’ R&D teams are also combining their intellectual resources, to develop screens for numerous diseases, including beta-globin analysis for sickle cell disease, alpha-1 antitrypsin deficiency, nepharopathic cystinosis, and hereditary hemachromatosis, as well as several genetic mutations related to hearing loss.
“Primary molecular screening [of newborns] has been discussed for years; however, an adequate platform was never available,” said Steven Dobrowolski, Telechem/ Arrayit.com’s chief scientific officer.
Dobrowolski and Mark Schena, a microarray pioneer and Telechem/ Arrayit.com’s current visiting scholar, have solved this problem by developing what Dobrowolski calls “a simple, yet elegant DNA microarray platform designed to accommodate high-volume, high-throughput genetic screening at a previously thought unattainable low cost.”
The company said it would provide the 15 hearing loss screens for about $35 per infant, compared to the current molecular mass spectrometry tests that cost between $500 and $1,500 per child.
To provide these affordable screens, NGS-Arrayit uses a microarray platform that turns the traditional gene expression paradigm on its head. Instead of spotting down thousands of different nucleotide probes on one chip to test one sample for expression levels of thousands of different genes, “we print the same genetic region for thousands of different individuals,” on one chip, said Robin Stears, Telechem/ Arrayit.com’s microarray scientist.
The spots on the array contain amplified DNA, not RNA, and derive from dried bloodspots collected from the newborn at birth. The company uses technology developed by Schena to select certain chromosomal loci surrounding a particular single nucleotide polymorphism, and individually amplify the region before spotting it down on a Telechem super amine slide.
This method currently allows NGS-Arrayit to spot down 3,500 different DNA samples on a slide, but the company hopes to work up to 10,000.
To label these DNA samples, the company also uses a distinctive method invented by company scientists. Instead of adding one or two fluorescent labeling molecules on each sample, the company adds dendrimers, “little balls of oligos that have either 250 Cy3 or 250 Cy5 molecules on them — or we can do four-color detection with Alexa dyes as well,” said Stears.
These dendrimers, which Stears detailed in a Physiological Genomics article published in September 2000, apparently give off a signal which is, not surprisingly, 250 times as strong as that of the standard one-or-two molecule fluorescent labels.
“It’s like using a halogen lamp instead of a candle,” said Stears. “The signal-to- noise ratios are log orders above ordinary standard detection methods.”
NGS-Arrayit is still working on empirically determining the optimal hybridization conditions for different oligonucleotides on its arrays, said Stears.
Once the technical hurdles are cleared, the company has to scale the process up and implement it as a clinical screen. NGS-Arrayit does not need to get its tests approved by the FDA because the test itself does not provide diagnostic information: The doctor has to diagnose based on the results of the screens, according to Stears.
This clinical screen, which NGS-Arrayit hopes to have up and running for the state of New Jersey’s mandatory neonatal screening program by January 1, 2002, and for Oz Systems within nine months, could prove to be the first real-world testing ground for a technology so far confined to research labs. While this mass application of microarray technology has its risks, NGS-Arrayit scientists are very optimistic that it will prove successful.
“Newborn screening, where literally many tens of thousand of assays are required on a daily basis, will serve to prove the microarray platform as a powerful tool for medical purposes,” said Dobrowolski. “Indeed, this will be one of the great pay-offs of the Human Genome initiative,” Dobrowolski said.