The latest research progress of CRISPR / CAS in May 2020

< br / >CRISPR is the abbreviation of regularly spaced short palindrome repeats, and CAS is the abbreviation of CRISPR related proteinsCRISPR / CAS was originally found in < br / > bacteria < br / > and was used to identify and destroy defense systems against phage and other pathogens< br / > < br / > the picture is from Thomas splattstoesser (Wikipedia, CC by-sa 4.0)< br / > on November 26, 2018, he Jiankui, a Chinese scientist, claimed that the world's first genetically edited baby, a pair of twin female babies, was born in NovemberHe used crispr-cas9, a powerful gene editing tool, to modify one gene of the twins so that they can naturally resist HIV infection after birthThis is also the world's first immune AIDS gene editing babyThe news was quickly fermented on websites at home and abroad, triggering thousands of wavesSome scientists support he Jiankui's research, but more are questioning, even condemning< br / > < br / > What are the major CRISPR / CAS studies or findings in the coming May? The editor combed the CRISPR / CAS research news reported by Biovalley this month for you to read< br / > 1< br / > many researches have developed a new CRISPR / cas9 tool that can enhance the editing scope of genome < br / > doi:10.1038/s41467-020-16117-8;doi:10.1038/s41587-020-0517-0;doi:10.1126/sciadv.aau0766 CRISPR has become one of the most promising genomic editing tools for its application range from the treatment of genetic diseases to the nutritional efficacy of cropsHowever, cas9 enzymes rely on specific DNA zip codes to determine where to cut and editAlthough cas9 (spcas9) from Streptococcus pyogenes is the most widely used, it requires two g-bases beside the target siteLess than 10% of DNA sequences meet this requirement < br / > < br / > in two new studies published in Nature Biotechnology and nature communications in May 2020, researchers from Massachusetts Institute of technology and other research institutions in the United States have successfully designed new proteins with enhanced genome editing ability, thus greatly expanding the DNA sequence that can be accessed accurately and effectively The two studies were conducted by pranam Chatterjee, who just completed his Ph.D in the media lab of MIT, and Joseph Jacobson, associate professor of the media lab of MIT, in collaboration with researchers from the University of Massachusetts School of medicine The titles of the papers are "an engineered sccas9 with broad PAM range and high specificity and activity" and "a cas9 with PAM recognition for adenine insights" < br / > picture from nature communications, 2020, doi:10.1038/s41467-020-16117-8 。 < br / > < br / > these new findings are due to the breakthrough achievements made by these authors in the calculation and discovery of cas9 protein They identified cas9 (sccas9) from Streptococcus canis and characterized it in experiments Although similar to spcas9, sccas9 has the ability to target DNA sequences more widely This discovery has expanded the targeting site of cas9 from 10% of the original genome to nearly 50% In 2018, they first reported the findings in the journal Science Advanced (science advanced, 24 OCT 2018, doi:10.1126/sciadv.aau0766 ）。 < br / > < br / > in order to improve the function of sccas9 as a genome editing tool, these authors found out the unique part from the similar cas9 protein through the calculation method, so as to design an optimized version of sccas9, which they named SC + + < br / > < br / > at the same time, these authors have successfully used their Spamalot algorithm, and found Streptococcus macacae cas9 (smaccas9), which needs two a bases instead of two G bases Through domain exchange and further gene transformation, they obtained a new ispymac enzyme as one of the first known cas9 editors that did not need g-base, so that they could further target 20% of the genome that could not be targeted before < br / > Chatterjee, in collaboration with the University of Zurich in Switzerland, is looking for final progress that will allow scientists to target any genome sequence and address any type of genetic mutation in the treatment of genetic diseases < br / > 2 < br / > FDA Approves CRISPR test of new coronavirus developed by Zhang Feng: 1 hour results, as convenient as pregnancy test paper! < br / > news source: < br / > shrelock based one-step test provides rapid and sensitive covid-19 detection < br / > < br / > < br / > < br / > CRISPR based new technology developed by Zhang Feng and others can provide the detection results of sars-cov-2 within one hour through one-step reaction Researchers shared the experimental scheme and toolkit to promote research and move forward to clinical verification FDA approved the technology on May 6 as an emergency test for clinical detection of new coronavirus < br / > < br / > a team of researchers from MIT's McGovern Brain Institute, MIT and Harvard's broad Institute, Ragon Institute and Howard Hughes Medical Research Institute developed a new diagnostic platform called stop (Sherlock testing in one pot) This test can respond in a single step with a minimum of processing in an hour, which makes the CRISPR based Sherlock diagnostic technology closer to a field or home test tool It works by programming CRISPR to detect the fragment of sars-cov-2 gene in nose, mouth, throat swab or lung fluid If the genetic material of the virus is found, CRISPR enzyme will emit fluorescence < br / > < br / > this new test is called "stopcovid" and is based on the stop platform In the research, it has been proved to be able to detect covid-19 virus sars-cov-2 quickly, accurately and highly sensitively The method is simple, requires little training, and uses simple and ready-made equipment, such as test tubes and water baths Stopcovid has been validated in the study, where researchers used a nasopharynx swab from a patient diagnosed with covid-19 As a proof of principle, sars-cov-2 RNA was added to saliva samples and then tested successfully < br / > 3 < br / > NAT Med weighs! It's safe to treat cancer with gene editing T cells! Huaxi Hospital, the world's first gene editing T cell treatment of cancer clinical trial results announced! doi:10.1038/s41591-020-0840-5 < br / > The results of the first human trial on cells using CRISPR gene editing technology published recently show that the therapy is safe and durable < br / > < br / > recently, the research team led by Professor Lu u from West China Hospital of Sichuan University reported the clinical trial results of the world's first gene edited immune cells on Nature Medicine, which reported the first phase of clinical trial results of crispr-cas9-mediated pd-1-edited T cells in patients with advanced non-small cell lung cancer（ ClinicalTrials.gov NCT02793856)。 The primary end point of the study was safety and feasibility, and the secondary end point was effectiveness The goal of the exploration includes tracking the edited T cells The results show that all the pre-determined endpoints are satisfied < br / > In general, PD-1 protein will signal to prevent immune cells from attacking human tissues, while active PD-1 will open the door of cancer spread < br / > < br / > 22 patients were included in this study; 17 of them obtained enough edit T cells for infusion, and 12 were able to receive treatment The researchers found that all treatment-related adverse events were 1 in 2 The edited T cells can be detected in peripheral blood after transfusion The presence of the edited T cells in the blood for at least four weeks suggests that this strategy may have a lasting effect The median progression free survival was 7.7 weeks (95% confidence interval, 6.9-8.5 weeks) and the median overall survival was 42.6 weeks (95% confidence interval, 10.3-74.9 weeks) The researchers sequenced the next generation of 18 candidate sites and found that the median mutation frequency of miss events was 0.05% (range 0-0.25%) < br / > 4 < br / > nature: identifying new T cell immunotherapy targets is expected to help develop new therapies against cancer and autoimmune diseases < br / > doi:10.1038/s41586-020-2246-4 < br / > < br / > recently, a research report titled "CRISPR screen in regulatory T cells reeals modulators of Foxp3" was published in the international journal Nature, Scientists from the University of California and other institutions said through research that crisrp screening of regulatory T cells may be expected to reveal the regulator of Foxp3, which is one of the key transcription factors controlling the development and function of Treg cells (regulatory T cells), and it is an important progress in Treg immunobiology, It also opens a door for scientists to further understand the function and mechanism of Treg < br / > Image Source: frontiers < br / > < br / > in this study, the researchers developed a CRISPR based joint screening platform for the phenotypic study of primary mouse Treg cells At the same time, the researchers used this technology to screen and analyze about 500 and nuclear factors for targeted function loss, so as to identify gene regulatory programs that can promote or interfere with Foxp3 expression According to researcher Jessica T Cortez, we have found several regulators of Foxp3 expression, including ubiquitin specific peptidase 22 (USP22) and ringfinger protein 20 (rnf20); USP22 is a member of the ubiquitination module of Saga chromatin modified complex, which can be used as a forward regulator to stabilize Foxp3 expression However, screening results show that as E3 ubiquitin ligase, Rnf20 can be a negative regulator of Foxp3 < br / > < br / > according to the researchers, the Treg of USP22 in mice can specifically eliminate or reduce the level of Foxp3 protein and induce the loss of its inhibitory function, which leads to the production of spontaneous autoimmune response, but it can protect the body against the growth of tumor in a variety of cancer models; in the Treg cells with USP22 deficiency, Foxp3 is unstable or can be saved by the removal of rnf20, This suggests that there may be a ubiquitination switch in Treg cells < br / > < br / > < br / > 5 < br / > nature breakthrough: using CRISPR to achieve high-throughput detection of viruses, 169 viruses are detected at a time! doi:10.1038/s41586-020-2279-8 < br / > < br / > researchers have developed a new technology that can flexibly expand CRISPR based molecular diagnostics, and can run thousands of tests at the same time using microfluidic chips The capability of a single chip can range from detecting a single type of virus in more than 1000 samples at a time to searching more than 160 different viruses in a small number of samples, including covid-19 virus < br / >