Posted on Aug 05, 2018, 8 p.m.
CRISPR-Cas9 gene editing systems are very promising for their potential to treat diseases caused by gene irregularities, off target effects threaten to delay its development. University of Texas scientists are proposing replacing Cas9 protein with Cas12a may address CRISPR’s shortcomings, as published in the journal Molecular Cell.
The Cas9 protein can be considered the scalpel as it cuts the strands of DNA in CRISPR processes. Unfortunately sometimes it edits the wrong part of the genome which disturbs healthy functions rather than fixing disease causing genes, which is feared might inadvertently cause healthy cells to turn cancerous, fears that were compounded with 2 recent studies suggesting even targeted cells that are successfully edited can be more susceptible to cancer causing mutations.
According to the scientists they have found that the difference between Cas9 and Cas12a is in binding behaviors; Cas9 binds like superglue to targets, and Cas12a binds more like a velcro. Cas9 latches on to the first few letters of a target but stops there, if there is a mismatch later in the DNA strand it may get overlooked and the wrong section of the genome may be edited. Cas12a checks each pair base in targets before moving on making it possible to correct mistakes as demonstrated by the scientists in their research findings.
CRISPR safety concerns have prompted scientists to propose various methods from improving the promising technology. Stanford University and the National Institute of Standards and Technology have recently announced invention of a new gene editing system called MAGESTIC which is designed to improve the process by which edited DNA repairs itself. Scientists in Poland have said they are working on a version of CRIPSR using a variant of Cas9 to cut one DNA strand instead of two.
Safety concerns burden the CRISPR industry as a paper published in Nature Biotechnology has suggested Cas9 could cause undetectable genetic changes, a prospect which may delay human trials of CRISPR that are expected to start late 2018.
Cas12a has been suggested by other research teams to possibly be more precise than Cas9 in the past, it is not a new discovery, but previous evidence was inconclusive according to the scientists at the University of Texas who believe further development of Cas12a may make an error proof gene editing system possible.
Cas12a is a better protein in general but some areas still are blind to some mispairing between RNA and genomic targets, what their work does is show a path forward towards improving Cas12a and gene editing further says Ilya Finkelstein assistant professor of molecular bioscience at the University of Texas, Austin.
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