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Startup Twistnostics Developing Rapid Microarray Platform for PGx and Infectious Disease Assays

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With a $150,000 grant from the National Human Genome Research Institute, startup Twistnostics is hoping to demonstrate the potential of its single-molecule array technology to support rapid multiplex molecular diagnostics.

In a pilot project funded by the NHGRI grant, Twistnostics hopes to demonstrate that its so-called Twist-Biosensors can detect three SNPs in the CYP2D6 gene associated with variations in human drug metabolism. The firm intends to then develop the technology to support the creation of 50- to 100-SNP microarrays for pharmacogenomic genotyping and use in other diagnostic areas like infectious disease and early cancer detection.

Alfredo Celedon, Twistnostics' founder, told BioArray News that the company's approach is based on work he did as a graduate student at Johns Hopkins University, where the company is now located in an incubator space.

"The Twist-Biosensor is a single molecule of DNA that we use to detect the presence of other DNA molecules in a sample. The DNA molecules are bound to a flat surface and when hybridization takes place, [they] give a strong electrical signal that we can detect," Celedon explained.

"At Johns Hopkins, I was studying the mechanical properties of DNA — how much force you need to apply to stretch the molecule, for example … Using that background, we came out with an idea of a biosensor based on a single DNA molecule," he said.

While traditional microarray technologies rely on applying stringency conditions based on temperature or buffer, Celedon said his company's Twist-Biosensor array relies on applying torque or physical twisting force to its target to make hybridization more specific.

"This works much more quickly and more accurately" than other approaches, he said. "It allows us to have our result in hours — for something that would take days with normal microarray techniques … A typical microarray can genotype millions of SNPs but it takes three days to do that process," he said, "and still the specificity and sensitivity of each SNP is far from 100 percent."

In the company's NHGRI-funded study, Celedon's team plans to develop a prototype device based on its Twist-Biosensors to detect three CYP2D6 SNPs associated with drug metabolism variation in blood samples.

"This project is basically a demonstration of the technique," he said. "Moving forward, our overall goal is to develop a handheld device that we can use for rapid genotyping of hundreds of SNPs at a time."

According to Celedon, Twistnostics believes that there are many areas where its technology could be applied.

He said that the company's goal in the pharmacogenomics space is to develop a menu of different chips for rapid PGx genotyping, each focused on a particular gene and its associated drug or drugs.

"The idea is that a doctor, before dosing a drug to a patient, can run a quick test and in this way dose the right amount," Celedon said. "Right now [doctors] use averages, saying an average patient needs this amount, to make dosage decisions, but that is not precise and it can be dangerous in some cases," he said.

Celedon added that the "variability of the enzymatic activity is such that the same amount of drug can produce an adverse drug reaction in some patients and have no therapeutic effect in others"

Following the recently funded pilot project, Twistnostics' goal is to develop a chip able to genotype about 50 SNPs covering most of the polymorphisms of CYP2D6, Celedon said. "Then our plan is to develop chips for other enzymes that are related to other drugs … so we would not be putting thousands of SNPs in one chip, but more like 50 to 100 that are relevant for one specific condition."

According to Celedon, the company is also currently working to develop a rapid test for respiratory viruses based on the Twist-Biosensor technology, and is also planning to work on a test for bacterial drug resistance.

A third goal would be to apply the technology to early cancer diagnosis, he said.

Though the company is still taking its first steps, he said the hope is that it will begin commercializing a first product in 2015.

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