Release date: 2017-10-27
Recently, two major groundbreaking studies have been reported in Nature and Scinece. One led by the Zhang Feng team discovered new molecules for editable RNA, while another study was led by the MIT Institute of Research and the Harvard University in Cambridge, Massachusetts, and the laboratory of Professor David Liu: New Gene Editing System!
Nature: New editing technology! Base exchange without DNA breaks!
Developed by MIT's extensive research institute and Harvard campus in Cambridge, Massachusetts, Professor David Liu led the development of a new genetic editing system! Unlike the original CRISPR gene editing system, this is a relatively unpredictable and flat molecular scissor form that cuts a significant portion of DNA—rewriting a single letter or genetic gene to have a single gene that can be altered ability.
And that means researchers can now try to correct more than half of human hereditary diseases!
This article was published in the October 25th issue of "Nature". Professor David Liu published an article entitled "Programmable base editing of A?T to G?C in genomic DNA without DNA". Layer waves!
Nature Report
In this article, a novel adenine base editor (ABE) is reported. Combined with previous techniques, ABE can convert A-T base pairs into G-C base pairs, or G-C bases. Convert to T-A base pairs!
Getting to the point of mutations
Base editors borrow from CRISPR's components—guide RNAs (gRNAs) and Cas9 or other nucleases—but don't cut the double helix and instead chemically alter single bases with deaminase enzymes such as TadA and ADAR.
Where is the breakthrough in this technology?
ABE enables the replacement of four different A, T, G, and C bases in DNA without relying on DNA fragmentation! This new type of technology has an inestimable effect on diseases caused by mutations in base pairs in human genetic diseases!
ABE editing technology
In this study, in human embryonic kidney cells and bone cancer cells, the technique was calibrated by researchers with about 50% efficiency and few detectable by-products! In contrast, the more traditional CRISPR-based approach, in which scientists insert DNA strands with the desired base changes, fixes the same single base difference by less than 5% efficiency, and often causes undesirable developments during editing. Insertion or deletion of bulk DNA.
Jin-Soo Kim, a molecular geneticist at Seoul National University, said: "This is a major breakthrough in the field of genome editing!"
Dana Carroll, a genetic engineering researcher at the University of Utah in Salt Lake City, said: "This represents a heroic effort. He pointed out that directed evolution is a shot in the dark. Carol said: "I won't Have the guts to try what they do. â€
The four types of capabilities of “A to G, G to A, C to T and T to C†will be very valuable for precise treatment and gene editing,†Plant Genetics, Institute of Genetics and Developmental Biology, Beijing Academy of Sciences, China Said Caixia Gao.
"Scinece": Zhang Feng team breaks through again, RNA edits new scissors!
On October 25th, US Eastern Time, the international academic journal Science published an article by Zhang Feng team introducing the new REPAIR system. The basic element of "REPAIR" is an enzyme named PspCas13b and an ADAR2 protein. "REPAIR" efficiently repairs individual nucleosides of RNA and is safer without changing DNA information, providing a new tool for basic research and clinical treatment.
Science report
The Cas13 enzyme family has recently been favored by the Zhang Feng team. On October 4th, in a paper published in the journal Nature, Zhang Feng team confirmed that another enzyme, Cas13a, can specifically down-regulate the levels of endogenous RNA and reporter RNA in mammalian cells.
“The primary goal of genetic editing is to correct mutations that cause disease. Now we are very good at inactivating genes, but it is much more challenging to repair lost protein functions. The new skill of editing RNA opens up more Probably, it can repair protein function in almost all cells and help a variety of diseases," said Zhang Feng.
Unlike the previous CRISPR system used to edit DNA, the Zhang Feng team found the PspCas13b enzyme in Prevotella. This is the "staple" of the Cas13 enzyme family that disables RNA and is a potential RNA "scissor".
But the "mission" that the Zhang Feng team gave to PspCas13b was not to inactivate RNA. Instead, they designed the "variation" of PspCas13b. This "variant" loses the function of "scissors" but is firmly bound to specific RNA fragments. At the same time, the partner of PspCas13b "variant" - ADAR2 protein will replace the adenosine nucleoside (A) on the fragment with inosine nucleoside (I).
Why do you want to do this replacement? It turns out that the mutation of guanosine nucleoside (G) into adenosine nucleoside (A) occurs, and this is considered to be closely related to diseases such as Duchenne muscular dystrophy and Parkinson's disease.
Many of human disease information is encoded in the DNA "life script." The emergence of gene editing technology has enabled scientists to modify DNA and bring hope to cure diseases. But because genes carry the most fundamental information of life, there are security and ethical concerns about editing DNA.
RNA editing is different. RNA is a genetic information vector using a single strand of DNA as a template. DNA sends out "wrong instructions", which are transcribed by RNA, translated into proteins and perform functions, in order to have disease manifestations. If you intercept it midway, correct the error message on the RNA, and let the protein receive the correct information, it can have a therapeutic effect.
Zhang and Liu emphasized that it may take several years for basic editing treatment to enter clinical trials, and it is also necessary to determine whether the method has advantages over existing gene therapy. However, it has become clear that powerful variants of standard CRISPR are already present in today's gene therapy systems.
Have to say: genetic editing makes the future full of possibilities!
Reference material
1, CRISPR hacks enable pinpoint repairs to genome
2, Novel CRISPR-derived 'base editors' surgically alter DNA or RNA, offering new ways to fix mutations
3, New Version of CRISPR, Developed by Feng Zhang-Led Team, Can Target and Edit RNA
4, Programmable base editing of A?T to G?C in genomic DNA without DNA cleavage
Source: Translational Medicine Network (micro signal zhuanhuayixue)
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