E. coli., the bacterium in which CRISPR-Cas was first observed.

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E. coli., the bacterium in which CRISPR-Cas was first observed.

October 16, 2017

Insight Into Jumping Gene Mechanisms to Advance Gene Editing

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Apocalyptic movies often cast a dark view of the future of gene editing.

In reality though, improved gene editing methods could be used to treat cancer, hepatitis B and other diseases. Though the technology is still in its nascent stages, new research out of the lab of Prof. Joseph Peters, microbiology, sheds light on new mechanisms that could be exploited to carry out more robust gene editing. Peters’ team found that transposons, or ‘jumping genes’, use a bacterium’s primary defense mechanism, CRISPR-Cas, to efficiently jump within the genome.

Jumping genes are sequences of DNA that can change their positions within the genome. About 33 to 45 percent of the human genome consists of such elements and though they can be beneficial for some species, jumping genes often alter the genome in ways that result in diseases in humans.

Recent studies have advanced our understanding of CRISPR-cas to the point that scientists have begun to use the procedure to edit genetic material in laboratories. The system was first identified in the bacterium E. coli. When a bacteriophage, a bacterial virus, infects a bacterium, the bacterium’s CRISPR-Cas system generates a protein that acts like molecular scissors to break the viral DNA. This allows the bacterium to copy and remember this piece. The next time the same virus infects the cell, the system synthesizes so-called guide RNAs that act as the scissor’s guide to the DNA to ensure that it can be easily broken down and rendered harmless.

Peters’ team sought to find any matches between CRISPR-Cas systems and jumping genes.

“We found a match between the new CRISPR-Cas system and these transposons indicating that the CRISPR-Cas systems were ‘captured’ by the transposon. Within a few months, we were able to analyze guide RNAs that were contained with these systems. This provided the ‘smoking gun’ that it was not being used primarily for defense but as a roadmap to travel to new bacterial hosts,” Peters said.

Consequently, the team discovered that this defense system was being “hijacked” and used by jumping genes to jump to new bacterial hosts.

According to Peters, the study has wide ranging implications. For one, it opens new possibilities for understanding how these systems work. Peters’ lab is working on proving that genes can be inserted wherever they choose using synthetic guide RNAs. In turn, this could be used in new systems to carry out more targeted gene modification in laboratories.

“A potential advantage of the system we are working on would be that any DNA could be introduced at a specific position. The transposon and CRISPR-Cas system would deliver this gene package to the specific site,” Peters said. “This could potentially reduce off-target effects where modifications are made elsewhere in the cell’s genome.”

Because jumping genes that are closely related to the ones the team explored act as cargo holds for 45 genes responsible for developing antibiotic resistance, their findings could also provide better ways of examining such outbreaks.