Meet the New Gene-Editing Technology: Prime Editing

 

Prime editing, a new entry in gene-editing technology, is said to be an extension of the “genetic toolbox.” According to a recent article in Science Daily, prime editing designs a more precise disease model while it corrects genetic problems.

The Comparison 

Scientists at Georgia’s Medical College report that both CRISPR and prime editing were successful at shutting down a gene involved in the maturing of smooth muscle cells.

But this is where the similarity ends. CRISPR’s double-strand cuts are sometimes harmful to cells and the system is occasionally responsible for unintended and broad edits going across the entire set of DNA (the genome).

Prime editing, however, only snips one strand of DNA.

CRISPR has three components:

  • The molecular scissors
  • Cas9, the RNA that guides the scissors to a target on the DNA; and
  • A template that repairs the problem

In comparison, prime editing only has two arms. It uses a modified Cas9 (Cas9 nickase) that makes a single cut in a DNA strand.

When CRISPR cuts both DNA strands (as also happens in nature) the error can be devastating. The cell must be mended immediately.

Genome editor Dr. Joseph Miano explains that prime editing is less complicated and more precise with fewer components when compared to CRISPR.

A Long History with CRISPR

Dr. Miano has been involved with CRISPR since 2013 when he worked with other scientists in altering the mouse genome. CRISPR, he explained, has the potential of curing sickle cell and other genetic diseases as well as lessening the harmful side effects of cancer which involves genetic and environmental factors.

Dr. Xiaochun Long is a molecular biologist. Along with Dr. Miano, she co-authored a comparative study of tetraspan-2 (Tspan2) which is a primary protein located on cell surfaces and is involved in smooth muscle cell changes. This was the second study published on the use of prime editing in mouse models.

In 2019 the journal Nature published the first report on prime editing. The report was prepared by Dr. David Liu, a chemical biologist, and his associate Dr. Andrew Anzalone. Dr. Liu recently co-authored a report on prime editing in mice that was published in Genome Biology.

Working as a Team

DNA has four base pairs: adenine, cytosine, guanine, and thymine. They can be matched in innumerable pairs that can be altered by gene-editing tools.

Drs. Long and Miano initially used CRISPR by creating a small change in a piece of DNA within the area of Tspan2. (a 3- base change). This is the standard method used by scientists to inactivate a gene’s control region.

The Tspan2 gene was turned off in the aorta and bladder of mice after CRISPR’s three-base change.

Prime editing was then used for a single-base change by making a single-strand break. Tspan2 was also turned off in the bladder and aorta by this small change but without damage by CRISPR.

One important difference was evident. The CRISPR cuts caused unintended deletions or insertions either near the intended edit or in other areas.

Dr. Miano mentioned that these unintended errors could result in curing one disease but creating another. At the conclusion of the study, the team saw no errors in the Tspan2 region or other locations.

The Bottom Line

Dr. Miano concluded that prime editing’s smaller cut of DNA is clean and snips without leaving collateral damage. He applauds the fact that there were no unexpected incidents and that the entire process was less complicated.

Looking Forward

The lethal megacystis-microcolon-intestinal hypoperistalsis syndrome affects muscles in the intestines and bladder, making it difficult for food to move through the GI tract or to empty the bladder. Dr. Allison Yang, a research assistant in the Miano lab, is planning to use prime editing for an in utero (before birth) correction of this disease.

Dr. Miano and his colleagues unintentionally created an almost perfect mouse model of this rare and lethal disease in an earlier work.

The long-term goal of the scientists is to prevent genetic abnormalities and diseases such as heart defects that necessitate major surgeries.

Rose Duesterwald

Rose Duesterwald

Rose became acquainted with Patient Worthy after her husband was diagnosed with Acute Myeloid Leukemia four years ago. He was treated with a methylating agent While he was being treated with a hypomethylating agent, Rose researched investigational drugs being developed to treat relapsed/refractory AML.

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