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According to the Perelman School of Medicine at the University of Pennsylvania, it is now possible to introduce targeted mutations in the genome by splitting specific mutant enzymes, and then trigger their recombination
.
Graduate student Kiara Berríos, under the guidance of Rahul Kohli, MD, associate professor of infectious diseases at the University of Pennsylvania, and Junwei Shi, Ph.
The base editor is one of the latest and most effective methods to achieve precise gene editing
.
In the DNA targeted by the base editor, the C:G base pair in the DNA can be mutated to T:A or A:T base pair can be converted to G:C
Researchers at the University of Pennsylvania discovered that DNA deaminase can be divided into two inactive parts, which can then be recombined using a small cell permeation molecule called rapamycin
.
The new split-engineered base editor (seBEs) system can be introduced and hibernate in the cell until small molecules are added, at which time the base editing complex can quickly "open" and change the genome
"Our newly created split-engineered base editor does provide new potential for research and treatment," said Coley
.
"Because we can control time variation, it is possible to use these Davidtz in vivo disease models to change genes, similar to how scientists control the timing of gene knockdown, and may even one day provide clinicians with the ability to control and edit patients' gene therapy.
"Splitting DNA deaminase can also work outside the base editor.
As a cancer researcher, I think this technology has the potential to control the genetic changes that lead to cancer development and growth
.
It can also be used to identify cancer cells.
Kohli and Shi’s laboratory plan to build on this research and apply controllable genome editing to cell-based screening studies, and add a layer of spatial control on the basis of time control
.
One advantage of the researchers' method is that the controllable split enzyme system can also be combined with other new developments in the rapidly developing CRISPR/Cas field to gain control over these different base editing strategies