Cell:blockbuster! Found targeted to the RNA of the CRISPR/CasRx

Source: Cell:blockbuster! Found targeted to the RNA of the CRISPR/CasRx

2018 3 December 24/bio ValleyBIOON/—most people have heard of CRISPR/Cas9 gene editing technology, it as targeting molecular scissors, cutting a pathogenic gene, and the use of health of the gene to be replaced. But DNA is only part of the story; many of thegeneticthe disease is caused by RNA, especially mRNA on the problems caused, wherein the mRNA is DNA transcribed to produce, the resulting mRNA via post-translation to produce protein.< p>now, in a new study, from the United States Shaq biological Institute researchers constructed a targeting RNA instead of targeting the DNA of the new tool, and use it to correction from a dementia patient cells in a protein imbalance, thus allowing them to recover to healthy levels. This is referred to as CasRx new tool for scientists to provide a powerful method to develop new gene therapy and Research Foundation of biological functions. Relevant research results in 2018 3 May 15, online published in Cell journal, The paper entitled“Transcriptome Engineering with the RNA-Targeting Type VI-D CRISPR Effectors”.
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in the human cell nucleus（gray）, targeting RNA CasRx（Magenta）, the pictures from the Salk Institute.
Thesis communication the author, Shaq Institute of Biology Patrick Hsu said,“bioengineers like nature of the detective, as in the DNA model in the search for clues to help solvegeneticdisease mysteries. CRISPR sparked genomic engineering for change, and we hope that will this tool from the Edit DNA extended to the editing of RNA.”< p>CRISPRbacteriathe immune system, containing many Defense enzymes, such as Cas9“molecular scissors”in. Including the Hsu, including the scientists has been the Cas9 transformation is a powerful DNA targeted gene editing tools.

Hsu team decided to search thebacteriathe genome to find capable of targeting an RNA of a novel CRISPR enzyme, and then for them to be genetically modified and used to solve the RNA and the protein produced.

for example, a given RNA can be at different levels on the expression, and it is with other RNA to maintain a balance between the maintenance of healthy function is vital. In addition, the RNA can be in a variety of ways to be alternatively spliced, resulting in a different protein, but RNA splicing problems can result, such as spinal muscular atrophy, atypical cystic fibrosis and frontotemporal dementia（frontotemporal dementia, FTD such as the disease. Therefore, targeting the toxic RNA or by the inappropriate alternative splicing generating RNA, the drug is likely to suffer from these types of destructive diseases of the patients have life-changing impact.

the thesis of the first author, Shaq biological researcher at the Institute of Silvana Konerman explains,“We first is to assume that different CRISPR systems may bebacteriaand their viruses in evolutionary arms race process specifically generated, which potentially make them capable of targeting viral RNA.”

Hsu team developed a calculation program, thereby in thebacteriaDNA database looking for the CRISPR system to the characteristics of the signal: the specific repeated DNA sequence mode. By doing so, they found a target to RNA of the CRISPR enzyme family, as they call it Cas13d it.

Hsu team realized that just like the Cas9 family as derived from different bacterial species Cas13d enzyme in their activity will be different, thus they were screened, in order toIdentified a can in the human cells to use the best Cas13d version. They found this the best version from a gutbacteria: yellowing of the rumen bacteria（Ruminococcus flavefaciens）XPD3002, which led them to name it for CasRx it.

Konermann said,“once we have the transformation of the CasRx in human cells work well, so we really want to speed it up.”

This means that the CasRx be transformed to the treatment of disease-related symptoms: in this study, refers to the neurodegenerative diseases frontotemporal dementia（FTD to. In this dementia, the two versions of the tau protein-also implicated in Alzheimer’s disease progress in the proportion of neurons losing balance. Hsu team of CasRx be genetically modified such that it targeted over-expression of the kind of tau protein version of the RNA sequence. They by the CasRx packaging into the virus, and it will be transported to the origin of the self-FTD patientsstem cellsgenerated by the neurons to achieve this. CasRx let tau levels back to a healthy level of efficiency of 80%.

with the targeting of RNA to the other technologies compared to CasRx due to a smaller size, which makes it easy it will be packaging to treatment-related viralcarrier, and high efficiency and has a unique nature, but also with RNA interference compared to does not produce significant off-target effects. Hsu team for their development of the tool may be used to explore RNA and protein features present on the new issues and developing treatments based on RNA and protein disease feel exciting. Biological Valley Bioon.com

reference:

Silvana Konermann, Peter Lotfy, Nicholas J. Brideau et al. Transcriptome Engineering with the RNA-Targeting Type VI-D CRISPR Effectors. Cell, Published online: March 15, 2018, doi:10.1016/j. cell. 2018. 02. 033

Published at Mon, 25 Mar 2018 09:47:35 +0000