New CRISPR-Chip Detects Genetic Mutations in Minutes

A device called CRISPR-Chip that can detect genetic mutations in minutes.

Image: UC-Berkley

A team of engineers at the UC Berkeley and the Keck Graduate Institute (KGI) of The Claremont Colleges have developed a device called CRISPR-Chip that can detect genetic mutations in minutes. The hand-held device was made by combining CRISPR with electronic graphene transistors.

The new CRISPR-Chip, which was described in the journal Nature Biomedical Engineering, could be used to rapidly diagnose genetic diseases or to evaluate the accuracy of gene-editing techniques. The team used the device to identify genetic mutations in DNA samples from Duchenne muscular dystrophy patients, reports Berkley News.

“We have developed the first transistor that uses CRISPR to search your genome for potential mutations,” said senior author Kiana Aran, an assistant professor at KGI who conceived of the technology while a postdoctoral scholar in UC Berkeley bioengineering professor Irina Conboy’s lab. “You just put your purified DNA sample on the chip, allow CRISPR to do the search and the graphene transistor reports the result of this search in minutes.”

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Graphene, built of a single atomic layer of carbon, is so electrically sensitive that it can detect a DNA sequence “hit” in a full-genome sample without PCR amplification.

“Graphene’s super-sensitivity enabled us to detect the DNA searching activities of CRISPR,” Aran said. “CRISPR brought the selectivity, graphene transistors brought the sensitivity and, together, we were able to do this PCR-free or amplification-free detection.” She hopes to soon “multiplex” the device, allowing doctors to plug in multiple guide RNAs at once to simultaneously detect a number of genetic mutations in minutes.

Professor Kiana Aran conceived of CRISPR-Chip while a postdoctoral scholar at UC Berkeley and developed it as an assistant professor at KGI (Photo credit UC Berkley)

So far, the CRISPR-Chip’s sensitivity was tested by using blood samples from Duchenne muscular dystrophy (DMD) patients. It successfully detected two common genetic mutations associated with the disease. Point-of-care diagnosis of genetic diseases is an obvious use for the chip, but other applications include drug sensitivity testing.

Co-author of the paper Professor Irina Conboy said the new device could be especially helpful for screening DMD, as the severe muscle-wasting disease can be caused by mutations throughout the massive dystrophin gene – one of the longest in the human genome – and spotting mutations can be costly and time-consuming using PCR-based genetic testing.

“As a practice right now, boys who have DMD are typically not screened until we know that something is wrong, and then they undergo a genetic confirmation,” said Conboy, who is also working on CRISPR-based treatments for DMD.

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Co-author Niren Murthy, professor of bioengineering, concluded:

“If you have certain mutations or certain DNA sequences, that will very accurately predict how you will respond to certain drugs,”

Sam Draper
April 1, 2019

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