KromaTid paints by (chromosomal) numbers

For a group of Colorado State University researchers trying to create a genetic paint kit, the a-ha moment came on the London tube.

For years, several CSU scientists had been working on developing a fluorescent paint that could highlight one side of a chromosome – known as a chromatid – and show abnormal patterns and sequence inversions. The possible links between such defects and diseases and genetic conditions are poorly understood, and the researchers were looking for a better way to analyze the tiny imperfections.

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While attending a conference in the UK, Andrew Ray, now a professor in CSU’s Department of Environmental and Radiological Health Sciences, suggested to his colleagues that they use the recently mapped human genome to guide their progress. The idea boosted the research, and the group’s company, KromaTid, has announced their first successful paint. The groundbreaking innovation could help detect and diagnose a wide range of medical situations, from cancer to infertility to arthritis.

KromaTid is a CSU spinoff company first created in 2007 with support from Colorado State University Research Foundation and NeoTREX, the enterprise arm of the university’s Cancer Supercluster, which focuses on research and product development. Terry Opgenorth, chief operating officer of NeoTREX, has served as an interim CEO for the startup business and, based on his past experience in pharmaceutical research and drug discovery with Abbott Laboratories, he believes KromaTid represents “the next generation” of genetic analysis, with potential applications in the fields of bioscience and medicine.

Clearer genetic picture

Researchers have spent decades trying to get clearer and more detailed pictures of chromosomes, structures of protein and DNA found in cells that store genetic information. Humans have 23 chromosomes, including an X or Y, which determines sex.

Dating back to the 1970s, scientists developed a technique known as G-banding that identifies sequences of chromosomes taken from blood by staining them. The process was a major advance, but it was difficult to analyze since it used light or dark shades, rather than a spectrum of colors.

Over time, more advanced and colored paints made of fluorescent DNA molecules were developed to mark individual chromosomes and to recognize and analyze abnormalities. Down Syndrome, for instance, occurs when a person has an extra copy of the 21st chromosome, which could be easily distinguished with the colored paint.

But as scientists delved deeper into our genetic makeup, they found more and more complex and minute details to explore. Of particular interest are the arrangements within individual chromosomes, which are divided into two sides like an “X,” each called a chromatid.

Through the 1990s, researchers at CSU, Los Alamos National Laboratory in New Mexico and elsewhere began working on paints that could mark individual chromatids.

“None of us were having a bit of luck doing it,´ said Susan Bailey, one of the founders of KromaTid and also a professor in CSU’s radiological health sciences department.

Then came that fateful day in London. Following the map of the human genome, the scientists could focus on specific genetic sequences. They began designing probes that could highlight individual spots along a chromatid, which culminated in the recent development of a paint that can mark one side of the third chromosome.

KromaTid plans to make kits to paint all 23 human chromosomes, and the technology could also be developed for other species, such as dogs, horses and wildlife.

The chromatid paint will reveal rearranged or inverted segments of chromosomes, which could correlate with radiation exposure. It can also help with both diagnosis and prognosis of cancer, genetic conditions and a variety of other medical scenarios.

“The reason we’re so excited – in addition to, 20 years later, we finally have the thing – is it’s going to let us get to the problem of inversion detection,” Bailey said. “Now we can start to really look at rearrangements within the chromosome itself.”

NASA funding

In its early stages, KromaTid received funding through a NASA small-business research grant. The national space agency is particularly interested in better understanding radiation exposure for astronauts. The more in-depth information could influence plans for long-term space missions and how astronauts prepare for incidents, such as solar flares that release high doses of radiation.

KromaTid’s next steps, according to Opgenorth, include hiring a full-time, dedicated CEO and developing vested interests and incentives for early employees of the company.

With the backing from NeoTREX and a second NASA grant for $600,000, the company has licensed its technology and has signed on consultants and a team of scientific advisers to guide more general product development for other industries.

“It’s a group of founders who are very interested in how to do this as a company,´ said Opgenorth. “And how to do it right.”

In addition to cancer and radiation detection, the inversions and rearrangements revealed through KromaTid could ultimately be linked to conditions and illnesses, such as hypertension and arthritis, that scientists and doctors now consider idiopathic, or of unknown causes and origins. One particularly promising application, Bailey said, could be for the detection of infertility and sterility.

“Our hope is that the business can really move forward, and get this into the clinics and the clinical side of genetics,” she said.