Latest research progress of CRISPR/Cas in February 2021

February 28, 2021 News/bioon.
com" target="_blank">bioon.
com" target="_blank">/---The genome editing technology CRISPR/Cas9 was listed as one of the top ten scientific and technological advances in 2013 by "Science" magazine, and it is highly valued by people.
In October 2020, Dr.
Emmanuelle Charpentier of the Max-Planck Institute for Pathogenology in Germany and Dr.
Jennifer A.
Doudna of the University of California, Berkeley, USA won the 2020 Nobel Prize in Chemistry for their contributions to CRISPR-Cas9 gene editing .

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CRISPR is the abbreviation of regularly spaced clusters of short palindrome repeats, and Cas is the abbreviation of CRISPR-related proteins.
CRISPR/Cas was originally found in bioon.
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Picture from Thomas Splettstoesser (Wikipedia, CC BY-SA 4.

0).

What are the major CRISPR/Cas research or findings in the coming February? The editor combed the CRISPR/Cas research news reported this month for everyone to read.

1.
Mol Cell: New gene editing technology allows CRISPR-Cas9 to edit DNA in sequence
doi:10.

1016/j.

1.

Bradley Merrill, co-corresponding author of the paper and associate professor of biochemistry and molecular genetics at the University of Illinois at Chicago School of Medicine, said, “One disadvantage of the currently available CRISPR-based editing systems is that all editing or cutting is done at once.
There is no way.
Guide them so that they happen sequentially one after another.
"

The new method developed by Merrill and colleagues involves the use of special molecules called guide RNAs (gRNAs) that guide the Cas9 enzyme inside the cell and determine the precise DNA sequence where Cas9 will cut.
They call their specially designed gRNA molecules "proGuide", which allow the use of Cas9 to perform programmed sequential editing of DNA.

2.
Interpretation of Cell papers! Reveal the metabolic mechanism that controls the production of memory T cells
doi: 10.

1016/j.

2.

Picture from Cell, 2021, doi:10.

1016/j.

3.
Nature interpretation! A new CRISPR technology may revolutionize gene therapy to treat human genetic diseases
doi:10.

1038/s41586-020-03086-7

3.

In the article, researchers have conducted research on childhood progeria, which is a genetic disease that causes rapid aging of children.
At present, the second generation of CRISPR gene editing technology developed by scientists-base editing (base editing) is already in development.
Successful tests have been carried out in the mouse body.
With the help of this technology, researchers may eventually correct human life-long genetic diseases, including childhood progeria.

4.
bioon.
com/article/6784395.
html" target="_blank">Genome Res: Scientists are expected to enhance the efficiency of CRISPR elimination technology
doi:10.

1101/gr.

4.
bioon.
com/article/6784395.
html" target="_blank">Genome Res: Scientists are expected to enhance the efficiency of CRISPR elimination technology
doi:10.
1101/gr.
265736.
120 bioon.
com/article/6784395.
html" target="_blank">Genome Res: Scientists are expected to enhance the efficiency of CRISPR elimination technology

Recently, in a research report titled "Enhancing CRISPR deletion via pharmacological delay of DNA-PKcs" published in the international journal Genome Research, scientists from the University of Dublin and other institutions revealed how to improve the efficiency of CRISPR through research.
CRISPR deletion (CRISPR-del, CRISPR deletion) is a new type of gene editing tool that can remove or cut specific DNA fragments in living cells with surgical precision, thereby helping scientists study a variety of organisms.
The functions of diverse but poorly understood non-protein-coding DNA elements are called "dark matter" in the genome by scientists.

CRISPR-del technology is very practical and has a very wide range of applications, such as from basic research to the development of final therapeutic methods; but the main obstacle it faces is its low efficiency, which limits its application and increases This reduces the workload of laboratory staff and reduces the sensitivity of screening applications.
In this study, the researcher Professor Rory Johnson and others began to find ways to improve the CRISPR elimination technology, and then they developed a new reporting system to identify factors that can improve the efficiency of the elimination.

5.
Cell Stem Cell: Using CRISPR/Cas9 and iPSC technology to construct the first acute myeloid leukemia progression model
doi:10.
1016/j.
stem.
2021.
01.
011

5.
Cell Stem Cell: Use CRISPR/Cas9 and iPSC technology to build the first acute myeloid leukemia progression model
doi:10.
1016/j.
stem.
2021.
01.
011 Cell Stem Cell: Use CRISPR/Cas9 and iPSC technology to build the first acute Myeloid leukemia progression model

In a new study, researchers from research institutions such as the Icahn School of Medicine at Mount Sinai in the United States constructed the first cell model to describe the evolution of acute myeloid leukemia (AML) from early to late.
By using gene editing technology to change the genes needed to turn cells into malignant tumor cells, they can identify potential therapeutic targets in the early stage of the disease.
The relevant research results were published online on February 10, 2021 in Cell Stem Cell.
The title of the paper is "Sequential CRISPR gene editing in human ipsCs charts the clonal evolution of myeloid leukemia and identifies early disease targets".

The co-corresponding author of the paper, Dr.
Eirini Papapetrou, associate professor of oncology sciences at Icahn School of Medicine at Mount Sinai, said, “We basically built a leukemia model from scratch that describes the characteristics of the molecular changes that are the basis for the progression of this disease.
Allows us to determine the earliest events that occurred in the process of its production.
These events can be used as therapeutic targets.
By constructing the first cell model that tracks the evolution of human leukemia, we believe that we have taken a step towards uncovering the cell biology of this disease.
An important step.
We have identified the molecular vulnerabilities that emerged early in the course of this disease, which may lead to the discovery of better biomarkers of AML and improved new therapies-these goals have proven to be difficult for medical science to achieve in the past.
.
"

6.
bioon.
com/article/6784137.
html" target="_blank">PNAS: Scientists have identified three key genes that can help determine the characteristics of gastric stem cells!
doi:10.
1073/pnas.
2016806118

6.
bioon.
com/article/6784137.
html" target="_blank">PNAS: Scientists have identified three key genes that can help determine the characteristics of gastric stem cells!
doi:10.
1073/pnas.
2016806118 bioon.
com/article/6784137.
html" target="_blank">PNAS: Scientists have identified three key genes that can help determine the characteristics of gastric stem cells!

Recently, in a research report published in the international journal Proceedings of the National Academy of Sciences, scientists from Kanazawa University and other institutions in Japan have identified three key genes through research, which may help determine the role of gastric stem cells.
Characteristics (stemness).
The human body is composed of approximately 60 trillion cells, which are renewed every day to maintain the homeostasis of the body’s tissues, especially the cells in the digestive tract can be renewed within a few weeks, thanks to the rapid proliferation of stem cells in each tissue , It plays a very important role in supporting cell function.

Tissue stem cells play a key role in a variety of phenomena such as tissue generation.
When they divide, they can recover from damage by producing differentiated cells.
Tissue stem cells can do this by producing the same cells (self-renewal) or by differentiating into other types of cells.
In this study, the researchers discovered the existence of gastric tissue stem cells that can express the Lgr5 gene.
Lgr5 can be used as a marker of gastric gland basal tissue stem cells in gastric tissue, and its stem cell characteristics are inhibited by the Wnt signaling pathway.
However, due to the technical difficulty of further confirmation in vivo, scientists are not clear about the molecular mechanism of tissue stem cells regulated by Wnt signaling.

7.
bioon.
com/article/6783815.
html" target="_blank">Cell: Use Cas9 to record the elapsed time and time information of biological events
doi:10.
1016/j.
cell.
2021.
01.
014

7.
bioon.
com/article/6783815.
html" target="_blank">Cell: Use Cas9 to record the elapsed time and time information of biological events
doi:10.
1016/j.
cell.
2021.
01.
014 bioon.
com/article/6783815.
html" target="_blank">Cell: Use Cas9 to record the elapsed time and time information of biological events

Biological responses are highly dynamic, especially in living cells.
Therefore, unexpectedly, the rate of this reaction in living cells may be stable enough to be used as a timepiece system.
DNA is the genetic material of life and has been proposed as a medium for recording information.
Although DNA has been used to record biological information and computational mathematical problems, it has not yet been used to record time information.

The picture is from Cell, 2021, doi:10.
1016/j.
cell.
2021.
01.
014.

Here, we found that the insertions produced by Cas9 and gRNA can occur at a stable rate compared with typical dynamic biological reactions, and the frequency of accumulated insertions is a function of time.
By measuring the frequency of indels, we have developed a CRISPR-Cas9-based synthetic biological system that can simulate recording and measuring absolute time from hours to weeks in cultured human and mouse cells and mouse skin cells in a replicable manner Methods.
These time records were performed in several cell types.
The promoter and delivery vehicle of Cas9 were different, and they were performed in both cultured cells and cells of living mice.
As an application, we recorded the duration and elapsed time of chemical exposure since the onset of heat exposure and inflammation, so our system can be used as a synthetic "DNA clock".

8.
Nat Commun: In heterochromatin, TALEN's editing efficiency is 5 times that of CRISPR-Cas9
doi:10.
1038/s41467-020-20672-5

8.
Nat Commun: In heterochromatin, TALEN's editing efficiency is 5 times that of CRISPR-Cas9
doi:10.
1038/s41467-020-20672-5 Nat Commun: In heterochromatin, TALEN's editing efficiency is CRISPR-Cas9 5 times

In a new study, researchers from the University of Illinois at Urbana-Champaign used single-molecule imaging technology to compare genome editing tools CRISPR-Cas9 and TALEN.
Their experiments showed that the editing efficiency of TALEN is five times that of CRISPR-Cas9 in the tightly compressed part of the genome called heterochromatin.
Fragile X syndrome, sickle cell anemia, β-thalassemia and other diseases are caused by genetic defects in heterochromatin.
The relevant research results were published in Nature Communications on January 27, 2021.
The title of the paper is "TALEN outperforms Cas9 in editing heterochromatin target sites".

The corresponding author of the paper and professor of chemical and biomolecular engineering at the University of Illinois at Urbana-Champaign, Huimin Zhao, said that this study adds to the evidence that a wider choice of genome editing tools is needed to target different parts of the genome.
Zhao said, "CRISPR is a very powerful tool that triggered the genetic engineering revolution, but it still has some limitations.
" (Bioon.
com)