A study led by researchers at the Keck Graduate Institute (KGI), UC Berkeley and Vilnius University demonstrated new disease-detection capabilities of a hand-held device based on CRISPR gene editing technology, a development that could lead to faster, portable genetic testing for diagnostics and research.
Scientists look to variations at a single point on a DNA sequence for signs of disease or disease risk. Point mutations can change an entire DNA sequence, leading to conditions such as color blindness, Tay-Sachs disease, cancer, sickle cell anemia and amyotrophic lateral sclerosis (ALS).
The researchers showed that the device, called CRISPR-SNP-Chip, could accurately detect single nucleotide polymorphisms (SNPs), or point mutations, in sickle cell and ALS diseases without the need to amplify the DNA. The device is described in a paper published Monday, April 5, in the journal Nature Biomedical Engineering.
“By eliminating the need for amplification and large optical instruments, our SNP-Chip will make SNP genotyping for these purposes readily accessible,” said study principal investigator Kiana Aran, an assistant professor at KGI and a visiting scientist at UC Berkeley’s Department of Bioengineering. “The ability to detect SNPs on a chip does not just get to the core of human health genetics, it also gives us valuable and actionable insight into areas like agriculture, industrial bioprocesses and even evolutionary change, such as mutations conferring resistance to antibiotics.”
Aran led this study in collaboration with Irina Conboy at UC Berkeley and Virginijus Šikšnys at Vilnius University in Lithuania. Aran is co-founder of Cardea Bio, a San Diego-based biotechnology company that provided the primary funding for this work. Other study co-authors include researchers from UC Irvine and CasZyme.
“This technology innovates the field of CRISPR diagnostics and opens an avenue for digital accurate detection of genetic diseases, even when only one copy of a gene is mutated and only in one nucleotide,” said Conboy, UC Berkeley professor of bioengineering. “This is also a new platform to quickly and conveniently optimize CRISPR machinery, reducing the need for tests in cells and in vivo.”
Building on earlier research of the CRISPR-Chip, the researchers used electronic transistors made from graphene to detect genetic mutations in minutes. DNA samples are placed on the chip, and thousands of CRISPR molecules scan for specific mutations. If CRISPR binds with the target, it creates an electrical charge that is detected by the device.
“Merging a diversity of CRISPR-Cas biology with electronics, SNP-chip opens up a whole new range of possibilities for diagnostic and research applications,” said Siksnys, an early CRISPR pioneer and professor at Vilnius University. “Using the Cas9 orthologue for SNP detection is just the tip of the iceberg of opportunities.”
This study comes nearly one week after researchers at UCSF, UC Berkeley and UCLA announced FDA approval to launch the first clinical trial of a CRISPR gene-correction therapy for patients with sickle cell disease. These advances illustrate CRISPR’s potential for game-changing developments in health and medicine.