Zhang Feng publishes new tool: Editing RNA to treat a variety of persistent diseases

as the first pioneer to use crispr, a gene editing system, in mammalian cells, Zhang Feng, a Chinese scientist at the Broad Institute in the United States, recently became interested in RNA editing, sending out two papers in a month in top academic journals.
October 25, EST,
, an international academic journal, published an article by Zhang Feng's team introducing CRISPR's new system, REPAIR. The basic components of "REPAIR" are an enzyme named PspCas13b and an ADAL2 protein. "REPAIR" efficiently repairs individual nucleosides in RNA, which are safer because they do not change DNA information, and will provide a new tool for basic research and clinical treatment.
Cas13 enzyme family was recently favored by Zhang Feng's team. In an October 4 paper published in the journal Nature, Zhang Feng's team confirmed that Cas13a, another enzyme, specifically lowers endogenetic RNA and reported RNA levels in mammalian cells.
" gene editing is to correct the mutations that cause the disease. Now, we're good at indesomning genes, but fixing lost protein function is much more challenging. The new skill of editing RNA opens up more possibilities for repairing protein function in almost all cells, helping to treat a variety of diseases. Zhang Feng said.
the CRISPR system used to edit DNA, Zhang Feng's team found PspCas13b enzymes in prevotella. This is the "best" in the Cas13 enzyme family that can deactive RNA, and is a potential RNA "scissors".
the "mission" given to PspCas13b by Zhang Feng's team was not to inastate RNA, but rather to design a "variant" of PspCas13b. This "variant" loses the function of "scissors" but is firmly integrated into specific RNA fragments. At the same time, the partner of the PspCas13b "variant", the ADAR2 protein, replaces the adenine nucleoside (A) on the fragment with the secondary jaundice nucleoside (I).
do this replacement? It turns out that ostrich nucleoside (G) mutations occur from time to time as adenine nucleosides (A), which are thought to be closely related to diseases such as Duchy muscular dystrophy and Parkinson's disease.
of human disease information is encoded in DNA, the "script of life." The ad technology of gene editing has made it possible for scientists to modify DNA, giving hope for a cure. But because genes carry information about the root causes of life, there are safety and ethical concerns about DNA editing.
RNA editing is different. RNA is a carrier of genetic information based on a single strand of DNA. DNA issues "wrong instructions" that are tweed by RNA, translated into proteins and perform functions to show the disease. If intercepted in the middle, correct the error message on the RNA, so that the protein receives the correct information, can play a therapeutic effect.。 The relationship between DNA and RNA.
security and flexibility are the advantages of "REPAIR". "REPAIR can repair mutations without tampering with the genome. And RNA degrades automatically, modifying it or reversible. David Cox, a student at Zhang Feng's lab and co-author of the paper, said.
to make "REPAIR" more mature, Zhang Feng's team optimized it to design a "REPAIR2" version that would reduce the number of detectable off-target times in transcription groups from 18,000 to 20. According to the introduction, "REPAIR2" on the target RNA editing efficiency of 20%-40%, up to 51%.
To test the potential of the "REPAIR" system for disease treatment, Zhang Feng's team synthesized mutations that cause Fankoni anemia and X-series renal-causing urinary collapse, and introduced these mutations into human cells, which were eventually successfully repaired at the RNA level through "REPAIR".
, Zhang Feng's team said it would continue to look for clues from nature and design additional accessories for more types of nucleotide repair. (Source: Wang Yingying, News)