CRISPR technology can be used to relocalize DNA

By SHIRLEY MARINO LEE | October 25, 2018

At first sight, a cell’s DNA may look like a jumbled piece of string; however, it is actually highly organized. Through the use of clustered regularly interspaced short palindromic repeats (CRISPR), a gene-editing tool, researchers have discovered that the location of DNA is as vital as the sequence of base pairs in regards to how parts of the genome work.

For a while, scientists hypothesized that DNA within chromosomes had the ability to move and reposition itself in ways that could alter the activity of the moving genes. However, not until recently did they find a way to prove this hypothesis.

Recently, bioengineers discovered a way to use CRISPR to move specific pieces of DNA from one part of the nucleus to another, as reported by Cell

In a study published in Science Magazine, researchers first attached the DNA to a protein that has the ability to selectively link up with another protein found only in the target location when prompted by a specific plant hormone known as abscisic acid. Then, the second protein holds the piece of DNA securely in place within the target location. The removal of the abscisic acid loosens the connection and frees the DNA.

Researchers were able to demonstrate the effectiveness of this technique by moving several gene pairs from central locations to locations at the edge of the nucleus. They also expanded on the demonstration of this technique’s usefulness by moving telomeres, or stretches of DNA found at the tips of chromosomes implicated in aging. 

Researchers found that moving the telomeres to the inner edge of the cell’s nucleus caused the cell to grow much slower and sometimes not at all. In contrast, when they moved telomeres closer to cajal bodies, which are aggregations of protein and genetic material that process RNA, the cell was observed to grow faster and divide sooner than it typically would have. As a result of these pieces of evidence, the researchers concluded that the position telomeres are found in is vital to maintaining the cell’s health and productivity.

This new technique is coined CRISPR-GO, where the added term GO stands for genome organization. It promises to open up opportunities to investigate the role of placement and the organization of genes, which could lead to a better understanding of the nucleus. 

In the future, CRISPR-GO will also hold the promise of helping scientists explore the possibilities of altering cell activity to slow aging or prevent disease.

At the Hopkins School of Medicine, the Seydoux Lab is actively conducting research with the aid of CRISPR. Geraldine Seydoux, the lab’s principal investigator, makes use of CRISPR-Cas9 to delete, replace or reprogram the genes within Caenorhabditis elegans, a transparent nematode that grows to be about one millimeter in length. 

The use of CRISPR has allowed Seydoux to edit genes in ways that have caused a worm to stop reproducing, to glow in the dark after combining its DNA with that of a jellyfish and to be unable to fight off foreign DNA by deleting a gene that allowed it to produce a spot to store RNA. 

“Using a tool like CRISPR to make any mutation we want, big or small, speeds up our ability to decode the genome, to figure out the function of every gene. That’s a major goal of biology,” Seydoux said in a press release. 

The press release also discussed how other groups at Hopkins are working with CRISPR. 

“A team at the Wilmer Eye Institute is using CRISPR to edit retinal ganglion cells that could be transplanted into a patient suffering from blindness caused by glaucoma or multiple sclerosis [and] a group in the Bloomberg School of Public Health is looking to modify mosquitoes so that the bug’s offspring won’t transmit malaria to humans.”

CRISPR’s main contribution has been to the field of genetic engineering because it has allowed for the development of new, more efficient methods to modify an organism’s genome. Through this faster, cheaper and more accurate technique for studying and editing DNA, the search for applications of this method to help treat or prevent diseases has been further motivated and encouraged.

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