UMMS scientists develop multicolored labeling system to track genomic locations in live cells
“Most people are using CRISPR for editing genomes. We are using it to label DNA and track the movement of DNA in live cells,” said research specialist Hanhui Ma, PhD, who coauthored the study with Thoru Pederson, PhD, the Vitold Arnett professor of cell biology and professor of biochemistry and molecular pharmacology.
Knowing the precise location of genomic elements in live cells is critical to understanding chromosome dynamics because the genes that control our biology and health do so according to their location in 3-dimensional space, said Drs. Pederson and Ma. For a gene to be transcribed and expressed, it must be accessible on the chromosome. Where DNA is positioned in the crowded nucleus plays an important role in everything from embryonic development to cancer.
Current technologies, however, are only capable of following, at most, three genomic locations at a time in live cells. Labeling more sites requires that cells be fixed by bathing them in formaldehyde, thus killing them and making it impossible to observe how the chromosome’s structure changes over time or in response to stimuli.
To overcome this technological hurdle, Pederson and Ma turned to CRISPR/Cas9. To tag specific locations along the genome using the CRISPR/Cas9 complex, they created a Cas9 mutation that makes the nuclease inactive so it only binds to the DNA and doesn’t cut the genome. Once deactivated, the CRISPR/Cas9 element is ferried to a specific location on the genome by a guide RNA that can be programmed by the researchers.
New delivery method boosts efficiency of CRISPR genome-editing system
The genome-editing technique known as CRISPR allows scientists to clip a specific DNA sequence and replace it with a new one, offering the potential to cure diseases caused by defective genes. For this potential to be realized, however, scientists must find a way to safely deliver the CRISPR machinery and a corrected copy of the DNA into the diseased cells.
MIT researchers have now developed a way to deliver the CRISPR genome repair components more efficiently than previously possible, and they also believe it may be safer for human use. In a study of mice, they found that they could correct the mutated gene that causes a rare liver disorder, in 6 percent of liver cells — enough to cure the mice of the disease, known as tyrosinemia.
“This finding really excites us because it makes us think that this is a gene repair system that could be used to treat a range of diseases — not just tyrosinemia but others as well,” says Daniel Anderson, associate professor in MIT’s Department of Chemical Engineering and a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science (IMES).
The University of Massachusetts is the five-campus public university system of the Commonwealth of Massachusetts.
The system includes four universities and a medical school. Across its campuses, the University of Massachusetts enrolls about 71,000 students.
The UMass system was ranked 56th in the world in 2010 by the Times World University Rankings. It was also ranked as the 19th best university in the world in the Times of London’s 2011 World Reputation Rankings. In 2012, the state of Massachusetts introduced $607 million in new bond funding to advance high-quality instructional and research facility projects throughout the UMass system.
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