Scientists Create Molecular Scissors For Crispr Genome-Editing

Posted: Dec 2 2015, 4:15am CST | by , Updated: Dec 2 2015, 4:24am CST, in Latest Science News


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Scientists Create Molecular scissors for Crispr Genome-Editing
The researchers used structural knowledge of Cas9 to guide engineering of a highly specific genome-editing tool. Courtesy of Ian Slaymaker/Broad Institute of MIT and Harvard
  • Researchers develop Breakthrough Genome-Editing Scissor Molecules

Researchers from Broad and MIT have developed breakthrough genome-editing scissor molecules.

The experts have shown what they are capable of at the microscopic level. Scientists from Broad and MIT have genetically engineered transformations in the CRISPR-Cas9 editing system. This has resulted in fewer errors in off-target editing.

The technique indeed requires extreme finesse and solves the matter of genome editing. The CRISPR-Cas9 allows for many changes at the DNA level of cells. Cas9 tends to radically modify the DNA at a site that is marked by RNA whose sequence mirrors that of the target site.

Cas9 can cut its target site with ease and efficacy. The only hindrance is that when it enters a cell, it cuts other sites that are not meant to be altered at all. Thus these unforeseen edits result in displaced genes which is troublesome to say the least.

Such diseases as cancer can be contracted as a result of this unintended gene displacement. Therein lay the crux. In a recent study, it was reported that by changing just three of the colossal number of amino acids that comprise the Cas9 enzyme one can reduce off-target editing till the point where it was close to zero.

The experts employed information regarding the Cas9 protein to decelerate off-target cutting which was quite a task. The thing is that DNA carries a negative charge.

And it binds to a notch in the Cas9 protein that has a positive charge. By substituting some of the positively charged notches on the amino acids with neutral ones the binding of off-target sequences would increase rapidly.

After several false starts, the experts at Broad and MIT found that mutations in three amino acids dramatically reduced off-target cuts. In fact, the ratio was so low that it could hardly be seen on the scanner.

The novel enzyme which has been named “enhanced” S. pyogenes Cas9 or eSpCas9 is an excellent nostrum for gene editing where specific changes are required. The new enzyme is being produced for labs on a global level.

The same approach might work in case of other enzymes or so it is hoped. Quick and deft genome editing is the stuff that dreams are made of. Yet it does raise tough moral and organizational questions having to do with what makes us human.

This brand new enzyme is not to be seen as a panacea for all ills for such is certainly not the case. Rather it might have limited uses depending on the nature of the field of genetics.

This study is published on Monday in Science.

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