Clustered regularly interspaced short palindromic repeats (CRISPR, pronounced crisper are segments of prokaryotic DNA containing short repetitions of base sequences. Each repetition is followed by short segments of "spacer DNA" from previous exposures to a bacteriophage virus or plasmid.
Known as CRISPR-Cas9, this technology has led to a breakthrough in genomic engineering. But unlike earlier tools for genome editing, such as zinc-finger nucleases and transcription activator-like effector nucleases (TALENs), the technology makes it much easier and faster for cancer researchers to study mutations identified by The Cancer Genome Atlas and test new therapeutic targets.
The recently developed CRISPR system relies on cellular machinery that bacteria use to defend themselves from viral infection. Researchers have copied this cellular system to create gene-editing complexes that include a DNA-cutting enzyme called Cas9 bound to a short RNA guide strand that is programmed to bind to a specific genome sequence, telling Cas9 where to make its cut.
What makes CRISPR so exciting is that it can be used to actually edit out defective genes in living animals
With early successes in the lab, many are looking toward medical applications of CRISPR technology. One application is for the treatment of genetic diseases. The first evidence that CRISPR can be used to correct a mutant gene and reverse disease symptoms in a living animal was published earlier this year. MIT scientists report the use of a CRISPR methodology to cure mice of a rare liver disorder caused by a single genetic mutation. They say their study (“Genome editing with Cas9 in adult mice corrects a disease mutation and phenotype”), published in Nature Biotechnology, offers the first evidence that this gene-editing technique can reverse disease symptoms in living animals. CRISPR, which provides a way to snip out mutated DNA and replace it with the correct sequence, holds potential for treating many genetic disorders, according to the research team..
Penn scientist Dr. Carl June pioneered the use of genetically modified T cells, called CAR-T's, as a cancer treatment. So far, researchers have used traditional genetic engineering to make the cells home in on the molecules that stick out of tumor cells. But that's less efficient and often less precise than CRISPR. Penn is reportedly seeking NIH approval to use CRISPR to edit out two genes in T cells. One, called PD-1, suppresses the ability of T cells to attack tumors. The other is a T cell receptor that can turn the body's natural defenses against itself. The medical significance of the proposal is not clear, since gene editing has already been used in humans — just not gene editing via the CRISPR-Cas9 system. (2)
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