Posted by on July 28, 2020 2:35 pm
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Nature sub-Journal:say goodbye to insulin injections,CRISPR screening to find Type 1 diabetes β-cell protection…

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type 1 diabetes T1D is an autoimmune disease, multiple in the Teens, by the own immune system of the islet β cell destruction leading to β cell loss leads to insulin deficiency, only through multiple daily injections of insulin to treat, not cure, the life of the patient depends on insulin injections for treatment.< br>there are currently several research teams to develop an effective differentiation method from human embryonic or induced pluripotent stem cells iPSC)differentiation can generate insulin in the β-like cells. These studies improved by the use of autologous stem cell-derived beta cell replacement T1D patient lost the beta cells of the possibility, this strategy has Unlimited provides a cell potential, at the same time also can avoid transplant rejection problems.< br>however, these methods still exist key barriers-in the absence of immunosuppression in the case of recurrent autoimmune rapid destruction of the transplanted β cells. Still can not successfully be induced T1D patients for β cells to produce tolerance in immunotherapy from animal models into humans.< br>to date, the most promising interventions are the use of anti-CD3 monoclonal antibody-teplizumab, this one by the American biopharmaceutical company Provention Bio the development of a single anti-drug, has recently been confirmed that can delay Type 1 diabetes T1D high-risk populations, the onset time of at least 2 years. But there is still a lack in the absence of extensive immune suppression in the case of reversal of Type 1 diabetes interventions.< br>7 月 27, Harvard Medical School Ethan Peng et al. in Nature sub-Journal of Nature Metabolism magazine published entitled: Genome-scale in vivo CRISPR screen identifies RNLS as a target for beta cell protection in type 1 diabetes research papers.< br>the study by in vivo CRISPR genome screening, successfully found the type 1 diabetes T1D in the β-cell protective put target. Inhibit the RNLS gene may be effective in protecting type 1 diabetes T1D the β cells.< br>the study also found that has been approved by the FDA the drug Pargyline, can inhibit the RNLS gene, is safe and effective to protect beta cells and prevent Type 1 diabetes T1D is.< br>This discovery is expected to solve the autoimmune rapid destruction of the transplanted β cells of the puzzle for the complete cure of Type 1 diabetes T1D, and say goodbye to a lifelong injection of insulin brought new hope.< br>

in order to overcome autoimmune rapid destruction of the transplanted β cells of the puzzle, the research team sought to determine whether the presence of the transplanted β cells to autoimmune destruction resistant to the genetic modification.< br>there are studies trying to by targeting a series of immune recognition associated genes, including antigen-presenting human leukocyte antigen, to produce an immunogenic low cells. Although this method is partially effective, but it needs to be completely eliminated to prevent infection and the formation of tumor immune surveillance, and therefore this method has a certain potential danger.< br>the research team speculated that there may be in not completely compromising immune surveillance in the case to prevent against β cell autoimmunity targeting the mutation. In order to verify this speculation, the research team used CRISPR genome-wide screening techniques, in the T1D mouse model using its own immune selective pressure in autoimmune diabetes in unbiased genome-wide search, to looking for beta cell survival modification factor.< br>

genome-scale CRISPR–Cas9 screening to determine the RNLS is the NOD mouse model of β cell survival modification factor.< br>for Type 1 diabetes T1D the β cell replacement therapy has become a reality, stem cell/β cell differentiation research advances allow the manufacture of billions of patient-derived beta cells for transplantation. This treatment strategy the key obstacle is the β cells to autoimmune susceptibility, only by broad immune suppression to eliminate.< br>In this study, the research team through the genome-scale CRISPR screening, found that a few mutations can make the beta cells in people with Type 1 diabetes T1D the host survival.< br>although this is in a mouse model for the screening, but from a strictly experimental screening to the minority candidate genes one of the RNLS, the gene has been genome-wide Association study(GWAS)confirmed people with Type 1 diabetes T1D related to it. From human genetics research supporting evidence to further validate the RNLS mutation on mouse and human β-cell protective effect. These data indicate that the RNLS gene is the cause of Type 1 diabetes T1D in the β-cell vulnerability modifying factor.< br>More importantly, the research team further found a has been FDA approved drugs–Pargyline, the drug capable of binding to and inhibiting the RNLS, the study showed that Pargyline can protect β cells and preventing the mice of diabetes, and having good security.< br>

all in all, the study team through the genome-scale CRISPR screening in Type 1 diabetes T1D)in a mouse model of screening to protect the β cell survival of mutations, and with human GWAS data were combined with analysis to determine the RNLS is a β-cell vulnerability modifying factor.< br>the study also found that can the FDA approved the drug Pargyline re-used to inhibit the RNLS gene, is able to protect β cells, prevention of diabetes.< br>papers link:
https://www.nature.com/articles/s42255-020-0254-1
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Published at Tue, 28 Jul 2020 18:35:22 +0000