genome engineering – BioQuakes

Biologists can now control genetic inheritance in mammals with a CRISPR/Cas9-based approach, which allows geneticists to alter parts of the genome by removing, adding or altering sections of the DNA sequence. Scientists have sought a way to make precise changes to the genome of living cells for a long time, and now they actually can. You may ask, what are CRISPR and CAS9? Why are they important? Simply put, “The functions of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) and CRISPR-associated (Cas) genes are essential in adaptive immunity in select bacteria and archaea, enabling the organisms to respond to and eliminate invading genetic material.” Thus, this recent discovery has created the groundwork for developing new ways to fight diseases. UC San Diego researchers are responsible for this breakthrough. First, they injected a mouse with an engineered active genetic “CopyCat” DNA element into a Tyroisinase gene. The Tyroisinase gene determines fur color. The CopyCat element “disrupts” both copies of the Tyroisinase gene, causing the mouse to have white fur instead of black. The CopyCat element, however, could not spread through a population by itself, unlike the CRISPR/Cas9 systems, which could. This approach, though, was effective only in female mice, not in male ones, likely because of timing differences in meiosis – “a process that normally pairs chromosomes to shuffle the genome and may assist this engineered copying event.” The findings are nonetheless a success. Scientists are optimistic they will be able to alter multiple genes and traits using the same techniques in the near future. Cooper, one of the researches, summed up their achievement nicely: “We’ve shown that we can convert one genotype from heterozygous to homozygous. Now we want to see if we can efficiently control the inheritance of three genes in an animal. If this can be implemented for multiple genes at once, it could revolutionize mouse genetics,” said Cooper. More importantly, these findings continue to speed up research into diseases like cancer and mental illness.

CRISPR-CAS9 — “How the genome editor works”

Scientists have now created a new method of using CRISPR genome editing, which would allow them to activate genetics without breaking the DNA. It could potentially be a major improvement in using gene editing techniques to treat human diseases. Currently, most of the CRISPR systems work by creating DSBs or Double strand Breaks in regions of the genome targeted for editing. Many scientists and researchers have opposed creating breaks in the DNA of living humans. So the Salk group tried their new method to treat diseases such as diabetes, kidney disease, and muscular dystrophy in the mouse models.

CRISPR has proved to be a powerful tool for gene therapy, but there are still many concerns regarding some mutations generated by the DSBs though the Salk group is able to get around that concern. Originally, Cas9 enzyme couples with guide RNA to create DSBs. But just recently, researchers have used a dead form of dcas9 to stop the cutting of DNA. DCas9 would couple with transcriptional activation domains, that turn on targeted genes. But it is still difficult to be used in clinical applications.

Salk group team combined dcas9 with bunch of activator switches to uncover a combination that would work even when the proteins are not fused with one another. These components all work together to influence endogenous genes. It would influence genetic activities without having to change the DNA sequence.

In order to prove the usefulness of this method, scientists used mouse models of acute kidney disease, type 1 diabetes, and a form of muscular dystrophy. They engineered their new CRISPR system to boost the expression of an endogenous gene that would reverse the symptoms of the disease. In all three cases, they reversed disease symptoms.

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Photo credit: Martyn Fletcher

BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: genome engineering

CRISPR/Cas9: A New Means to Alter Genes

CRISPR used to treat diabetes, kidney disease, muscular dystrophy

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