Frontiers in genome editing最新文献

{"title":"On-site and visual detection of sorghum mosaic virus and rice stripe mosaic virus based on reverse transcription-recombinase-aided amplification and CRISPR/Cas12a.","authors":"Junkai Wang,&nbsp;Xiuqin Huang,&nbsp;Siping Chen,&nbsp;Jiahao Chen,&nbsp;Zhengyi Liang,&nbsp;Biao Chen,&nbsp;Xin Yang,&nbsp;Guohui Zhou,&nbsp;Tong Zhang","doi":"10.3389/fgeed.2023.1124794","DOIUrl":"https://doi.org/10.3389/fgeed.2023.1124794","url":null,"abstract":"<p><p>Rapid, sensitive and visual detection of plant viruses is conducive to effective prevention and control of plant viral diseases. Therefore, combined with reverse transcription and recombinase-aided amplification, we developed a CRISPR/Cas12a-based visual nucleic acid detection system targeting sorghum mosaic virus and rice stripe mosaic virus, which cause harm to crop production in field. When the RT-RAA products were recognized by crRNA and formed a complex with LbCas12a, the ssDNA labeled with a quenched green fluorescent molecule will be cleaved by LbCas12a, and then a significant green fluorescence signal will appear. The entire detection process can be completed within 30 min without using any sophisticated equipment and instruments. The detection system could detect samples at a dilution of 10⁷, about 10⁴-fold improvement over RT-PCR, so the system was successfully to detect rice stripe mosaic virus in a single leafhopper, which is the transmission vector of the virus. Finally, the CRISPR/Cas12a-based detection system was utilized to on-site detect the two viruses in the field, and the results were fully consistent with that we obtained by RT-PCR in laboratory, demonstrating that it has the application prospect of detecting important crop viruses in the field.</p>","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"5 ","pages":"1124794"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9895793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10652547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Squid express conserved ADAR orthologs that possess novel features.","authors":"Isabel C Vallecillo-Viejo,&nbsp;Gjendine Voss,&nbsp;Caroline B Albertin,&nbsp;Noa Liscovitch-Brauer,&nbsp;Eli Eisenberg,&nbsp;Joshua J C Rosenthal","doi":"10.3389/fgeed.2023.1181713","DOIUrl":"https://doi.org/10.3389/fgeed.2023.1181713","url":null,"abstract":"The coleoid cephalopods display unusually extensive mRNA recoding by adenosine deamination, yet the underlying mechanisms are not well understood. Because the adenosine deaminases that act on RNA (ADAR) enzymes catalyze this form of RNA editing, the structure and function of the cephalopod orthologs may provide clues. Recent genome sequencing projects have provided blueprints for the full complement of coleoid cephalopod ADARs. Previous results from our laboratory have shown that squid express an ADAR2 homolog, with two splice variants named sqADAR2a and sqADAR2b and that these messages are extensively edited. Based on octopus and squid genomes, transcriptomes, and cDNA cloning, we discovered that two additional ADAR homologs are expressed in coleoids. The first is orthologous to vertebrate ADAR1. Unlike other ADAR1s, however, it contains a novel N-terminal domain of 641 aa that is predicted to be disordered, contains 67 phosphorylation motifs, and has an amino acid composition that is unusually high in serines and basic amino acids. mRNAs encoding sqADAR1 are themselves extensively edited. A third ADAR-like enzyme, sqADAR/D-like, which is not orthologous to any of the vertebrate isoforms, is also present. Messages encoding sqADAR/D-like are not edited. Studies using recombinant sqADARs suggest that only sqADAR1 and sqADAR2 are active adenosine deaminases, both on perfect duplex dsRNA and on a squid potassium channel mRNA substrate known to be edited in vivo. sqADAR/D-like shows no activity on these substrates. Overall, these results reveal some unique features in sqADARs that may contribute to the high-level RNA recoding observed in cephalopods.","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"5 ","pages":"1181713"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10278661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10067579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In search of an ideal template for therapeutic genome editing: A review of current developments for structure optimization.","authors":"Alena Shakirova,&nbsp;Timofey Karpov,&nbsp;Yaroslava Komarova,&nbsp;Kirill Lepik","doi":"10.3389/fgeed.2023.1068637","DOIUrl":"https://doi.org/10.3389/fgeed.2023.1068637","url":null,"abstract":"<p><p>Gene therapy is a fast developing field of medicine with hundreds of ongoing early-stage clinical trials and numerous preclinical studies. Genome editing (GE) now is an increasingly important technology for achieving stable therapeutic effect in gene correction, with hematopoietic cells representing a key target cell population for developing novel treatments for a number of hereditary diseases, infections and cancer. By introducing a double strand break (DSB) in the defined locus of genomic DNA, GE tools allow to knockout the desired gene or to knock-in the therapeutic gene if provided with an appropriate repair template. Currently, the efficiency of methods for GE-mediated knock-in is limited. Significant efforts were focused on improving the parameters and interaction of GE nuclease proteins. However, emerging data suggests that optimal characteristics of repair templates may play an important role in the knock-in mechanisms. While viral vectors with notable example of AAVs as a donor template carrier remain the mainstay in many preclinical trials, non-viral templates, including plasmid and linear dsDNA, long ssDNA templates, single and double-stranded ODNs, represent a promising alternative. Furthermore, tuning of editing conditions for the chosen template as well as its structure, length, sequence optimization, homology arm (HA) modifications may have paramount importance for achieving highly efficient knock-in with favorable safety profile. This review outlines the current developments in optimization of templates for the GE mediated therapeutic gene correction.</p>","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"5 ","pages":"1068637"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9992834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9097000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Insights in genome editing tools and mechanisms: 2022.","authors":"Chanjuan Jiang,&nbsp;Qunxin She,&nbsp;Hailong Wang","doi":"10.3389/fgeed.2023.1240576","DOIUrl":"https://doi.org/10.3389/fgeed.2023.1240576","url":null,"abstract":"Genome editing technologies are important tools for studying the specific functions of individual genes or modulating the expression of important genes in organisms for biological research. CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR associated) is the prokaryotic adaptive immune system that protects hosts from invading viruses and plasmids. CRISPR/Cas9 systems are the most frequently used type of genome editing tool, which is composed of the Cas9 nuclease and the guide RNA which directs Cas9 to the target DNA site by sequence complementarity. In natural systems, guide RNAs are composed of two separate RNA molecules, the CRISPR RNA (crRNA) and the transactivating crRNA (tracrRNA), which are commonly artificially fused together to yield a single guide RNA for genome editing (Jinek et al., 2012). In addition to CRISPR/Cas9, a variety of other CRISPR-Cas systems, such as CRISPR/Cas12a (Cpf1), have been developed to overcome the difficulties of genome editing at different loci in different organisms. Recently, several new CRISPR/Cas systems have been identified and employed for genome editing, some of which are bacteriophage origin (Al-Shayeb et al., 2022). In addition, efforts have continuously been made to optimize genome editing efficiency by different CRISPR/ Cas systems belonging to all six known types. Furthermore, CRISPR/Cas9 systems have been optimized for reducing their toxicity and for boosting knock-in efficiency in genome editing of primary human cells by using long single-stranded DNA homology-directed repair templates with short regions of double-stranded DNA containing Cas9 target sequences on both ends (Shy et al., 2023). This Research Topic is aimed to further explore the application of CRISPR/Cas genome editing tools in more biological systems and it includes four research articles. Three articles are under the category of Original Research, and one belongs to the Brief Research Report. Peanut (Arachis hypogaea L.) seeds are the source of our daily edible oil and are rich in monounsaturated oleic acid and polyunsaturated linoleic acid. Fatty Acid Desaturase 2 (FAD2) catalyzes the conversion of oleic acid to linoleic acid. Compared with linoleic acid, oleic acid has better oxidative stability and health benefits, but increasing oleic acid content by knocking out the FAD2 gene can lead to poor plant stress tolerance. The RY repeat element and 2S seed protein motif cis-regulatory elements in the 5′UTR of FAD2 genes have been suggested to have enhancer activity. Neelakandan et al. targeted these two cisregulatory elements of the FAD2 gene promoter by CRISPR/Cas9 to downregulate the expression levels of two homologous FAD2 genes in seed while maintaining normal OPEN ACCESS","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"5 ","pages":"1240576"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10367544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9872660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering and targeting host factors to counteract SARS-CoV-2 and coronavirus infections: insights from CRISPR approaches.","authors":"Zhifen Cui,&nbsp;Hongyan Wang,&nbsp;Yizhou Dong,&nbsp;Shan-Lu Liu,&nbsp;Qianben Wang","doi":"10.3389/fgeed.2023.1231656","DOIUrl":"https://doi.org/10.3389/fgeed.2023.1231656","url":null,"abstract":"<p><p>Severe respiratory syndrome coronavirus 2 (SARS-CoV-2) and other coronaviruses depend on host factors for the process of viral infection and replication. A better understanding of the dynamic interplay between viral pathogens and host cells, as well as identifying of virus-host dependencies, offers valuable insights into disease mechanisms and informs the development of effective therapeutic strategies against viral infections. This review delves into the key host factors that facilitate or hinder SARS-CoV-2 infection and replication, as identified by CRISPR/Cas9-based screening platforms. Furthermore, we explore CRISPR/Cas13-based gene therapy strategies aimed at targeting these host factors to inhibit viral infection, with the ultimate goal of eradicating SARS-CoV-2 and preventing and treating related coronaviruses for future outbreaks.</p>","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"5 ","pages":"1231656"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10372414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9906744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CRISPR library screening to develop HEK293-derived cell lines with improved lentiviral vector titers.","authors":"Brian J Iaffaldano,&nbsp;Michael P Marino,&nbsp;Jakob Reiser","doi":"10.3389/fgeed.2023.1218328","DOIUrl":"https://doi.org/10.3389/fgeed.2023.1218328","url":null,"abstract":"<p><p>Lentiviral (LV) vectors have emerged as powerful tools for treating genetic and acquired human diseases. As clinical studies and commercial demands have progressed, there has been a growing need for large amounts of purified LV vectors. To help meet this demand, we developed CRISPR library screening methods to identify genetic perturbations in human embryonic kidney 293 (HEK293) cells and their derivatives that may increase LV vector titers. Briefly, LV vector-based Human CRISPR Activation and Knockout libraries (Calabrese and Brunello) were used to modify HEK293 and HEK293T cells. These cell populations were then expanded, and integrated LV vector genomes were rescued by transfection. LV vectors were harvested, and the process of sequential transduction and rescue-transfection was iterated. Through this workflow, guide RNAs (gRNAs) that target genes that may suppress or enhance LV vector production were enriched and identified with Next-Generation Sequencing (NGS). Though more work is needed to test genes identified in this screen, we expect that perturbations of genes we identified here, such as <i>TTLL12</i>, which is an inhibitor of antiviral innate immunity may be introduced and multiplexed to yield cell lines with improved LV vector productivity.</p>","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"5 ","pages":"1218328"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10373892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9916116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined approaches for increasing fetal hemoglobin (HbF) and <i>de novo</i> production of adult hemoglobin (HbA) in erythroid cells from β-thalassemia patients: treatment with HbF inducers and CRISPR-Cas9 based genome editing.","authors":"Alessia Finotti,&nbsp;Roberto Gambari","doi":"10.3389/fgeed.2023.1204536","DOIUrl":"https://doi.org/10.3389/fgeed.2023.1204536","url":null,"abstract":"<p><p>Genome editing (GE) is one of the most efficient and useful molecular approaches to correct the effects of gene mutations in hereditary monogenetic diseases, including β-thalassemia. CRISPR-Cas9 gene editing has been proposed for effective correction of the β-thalassemia mutation, obtaining high-level \"<i>de novo</i>\" production of adult hemoglobin (HbA). In addition to the correction of the primary gene mutations causing β-thalassemia, several reports demonstrate that gene editing can be employed to increase fetal hemoglobin (HbF), obtaining important clinical benefits in treated β-thalassemia patients. This important objective can be achieved through CRISPR-Cas9 disruption of genes encoding transcriptional repressors of γ-globin gene expression (such as <i>BCL11A, SOX6, KLF-1</i>) or their binding sites in the HBG promoter, mimicking non-deletional and deletional HPFH mutations. These two approaches (β-globin gene correction and genome editing of the genes encoding repressors of γ-globin gene transcription) can be, at least in theory, combined. However, since multiplex CRISPR-Cas9 gene editing is associated with documented evidence concerning possible genotoxicity, this review is focused on the possibility to combine pharmacologically-mediated HbF induction protocols with the \"<i>de novo</i>\" production of HbA using CRISPR-Cas9 gene editing.</p>","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"5 ","pages":"1204536"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10387548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9922897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum: Establishment of an efficient protoplast regeneration and transfection protocol for field cress (<i>Lepidium campestre</i>).","authors":"Sjur Sandgrind,&nbsp;Xueyuan Li,&nbsp;Emelie Ivarson,&nbsp;Annelie Ahlman,&nbsp;Li-Hua Zhu","doi":"10.3389/fgeed.2023.1183791","DOIUrl":"https://doi.org/10.3389/fgeed.2023.1183791","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fgeed.2021.757540.].</p>","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"5 ","pages":"1183791"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10083697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9289493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: CRISPR and beyond: Cutting-edge technologies for gene correction in therapeutic applications.","authors":"Ayal Hendel,&nbsp;Rasmus O Bak","doi":"10.3389/fgeed.2023.1203864","DOIUrl":"https://doi.org/10.3389/fgeed.2023.1203864","url":null,"abstract":"Gene editing promises the ultimate cure for genetic diseases by directly correcting disease-causing variants. However, the first clinical trials have chased the “low hanging fruit” using editing strategies that rely on gene disruption by introducing double-strand DNA breaks that lead to insertions and deletions (indels) by the NHEJ pathway. Since NHEJ is constitutively active throughout the cell cycle and the default DNA repair pathway, this is by far the most efficient type of conventional gene editing as opposed to homology-directed repair (HDR). HDR relies on delivery of an exogenous repair template and this pathway is active only in the S and G2 phases of the cell cycle. These two parameters constitute challenges in clinical use of HDR since exogenous DNA is toxic in most therapeutically relevant cell types and since the inherent competition between NHEJ and HDR can be a bottleneck. However, HDR benefits from enabling precise edits to be made to the genome, thereby representing true gene editing with control over the outcome. Still, in both these modalities the DNA breaks are considered a potential source of genotoxicity due to the possibility of off-target edits and chromosomal aberrations such as translocations and chromothripsis. Next-generation gene editing tools like Base and Prime Editing that rely on DNA single strand nicking reduce the risk of such harmful events but are still limited in the scope of the edits they can generate (Anzalone et al., 2020). The newest types of editors based on CRISPR-associated transposases or CRISPR-directed integrases facilitate larger edits but are still under development and immature for clinical implementation (Yarnall et al., 2022; Tou et al., 2023). This rapidly developing toolbox is expected to broaden the application of CRISPR-based tools and other site-specific engineered nucleases to cure human disease. However, on this venture of realizing precise gene correction there are several unanswered questions and challenges to overcome, some of which we hope to address with this Research Topic on Therapeutic Gene Correction Strategies Based on CRISPR Systems or Other Engineered Site-specific Nucleases. This Research Topic covers a selection of contributions including significant scientific advances in precise genetic engineering as well as expert perspectives on recent advances. OPEN ACCESS","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"5 ","pages":"1203864"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10157280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9431310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Similar deamination activities but different phenotypic outcomes induced by APOBEC3 enzymes in breast epithelial cells.","authors":"Milaid Granadillo Rodríguez,&nbsp;Lai Wong,&nbsp;Linda Chelico","doi":"10.3389/fgeed.2023.1196697","DOIUrl":"https://doi.org/10.3389/fgeed.2023.1196697","url":null,"abstract":"<p><p>APOBEC3 (A3) enzymes deaminate cytosine to uracil in viral single-stranded DNA as a mutagenic barrier for some viruses. A3-induced deaminations can also occur in human genomes resulting in an endogenous source of somatic mutations in multiple cancers. However, the roles of each A3 are unclear since few studies have assessed these enzymes in parallel. Thus, we developed stable cell lines expressing A3A, A3B, or A3H Hap I using non-tumorigenic MCF10A and tumorigenic MCF7 breast epithelial cells to assess their mutagenic potential and cancer phenotypes in breast cells. The activity of these enzymes was characterized by γH2AX foci formation and <i>in vitro</i> deamination. Cell migration and soft agar colony formation assays assessed cellular transformation potential. We found that all three A3 enzymes had similar γH2AX foci formation, despite different deamination activities <i>in vitro</i>. Notably, in nuclear lysates, the <i>in vitro</i> deaminase activity of A3A, A3B, and A3H did not require digestion of cellular RNA, in contrast to that of A3B and A3H in whole-cell lysates. Their similar activities in cells, nonetheless, resulted in distinct phenotypes where A3A decreased colony formation in soft agar, A3B decreased colony formation in soft agar after hydroxyurea treatment, and A3H Hap I promoted cell migration. Overall, we show that <i>in vitro</i> deamination data do not always reflect cell DNA damage, all three A3s induce DNA damage, and the impact of each is different.</p>","PeriodicalId":73086,"journal":{"name":"Frontiers in genome editing","volume":"5 ","pages":"1196697"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10267419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9660025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}