No abstract

The CRISPR/Cas system, an innovative gene-editing tool, is emerging as a promising technique for genome modifications. This straightforward technique was created based on the prokaryotic adaptive immune defense mechanism and employed in the studies on human diseases that proved enormous therapeutic potential. A genetically unique patient mutation in the process of gene therapy can be corrected by the CRISPR method to treat diseases that traditional methods were unable to cure. However, introduction of CRISPR/Cas9 into the clinic will be challenging because we still need to improve the technology's effectiveness, precision, and applications. In this review, we first describe the function and applications of the CRISPR–Cas9 system. We next delineate how this technology could be utilized for gene therapy of various human disorders, including cancer and infectious diseases and highlight the promising examples in the field. Finally, we document current challenges and the potential solutions to overcome these obstacles for the effective use of CRISPR–Cas9 in clinical practice.

Background: Hyperphenylalaninemia (HPA) is an autosomal recessive disorder that results from a deficiency in the phenylalanine hydroxylase enzyme (PAH) or from a flaw in the genes that are responsible for the biosynthesis or regeneration of the cofactor tetrahydrobiopterin (BH4), including GCH1, SR, QDPR, PTS, and PCD. Identification of disease-causing variants in these genes can help physicians and clinical geneticists in differential diagnosis, appropriate prescription drugs, and saving time and cost. This study attempted to identify these genes' most prevalent disease-causing variants in Iranian HPA patients. Summary: This study was performed under the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Before it started, the flow work and inclusion/exclusion criteria were published as a protocol in PROSPERO (CRD42021273705). We conducted a comprehensive search on 10/12/2022 on international online databases, including Web of Science, Scopus, EMBASE, Science Direct, PubMed/Medline, Google Scholar, SID, ISC, and Magiran search engine, to find pertinent publications. Some studies were chosen based on inclusion and exclusion criteria. Altogether, 1243 Iranian patients from 13 articles were considered. In total, we identified 129 distinct disease-causing variants in PAH (20 novel variants), 29 in QDPR (17 novel variants), 15 in PTS (seven novel variants), and one novel variant in PCD. Twenty disease-causing variants for PAH, 18 for QDPR, and eight for PTS are included in the genes' proposed genetic diagnostic panels. These panels include more than 75% of the documented disease-causing variants in the Iranian population. Key Messages: The findings of this research illustrated the spectrum of disease-causing variants in the PAH, QDPR, PTS, and PCD genes identified in Iranian HPA patients. Common disease-causing variants of these genes may be chosen as a preliminary diagnostic panel for early diagnosis and lowering therapy costs.

BACKGROUND: Due to the diagnosis of gastric cancer in advance stages as well as its poor prognosis, finding biomarkers is essential.OBJECTIVE: In this study, using the TCGA RNAseq data of gastric cancer patients, we evaluated the diagnostic value of lncRNAs which had differential expression.METHODS: we evaluated P value, FDR, log fold change for whole transcripts. Next, by comparison of the RNAseq gene names with total known lncRNA names, we identified differntial expressed lncRNAs. Folowing, we calculated specificity and sensitivity for lncRNAs came from previous step. For more confirmation, we predict target genes and performed GO and KEGG signalling pathway analysis. At the end, we examined the reliability and consistency of expression of this signature in three gastric cancer cell lines and one of them in twenty tumoric and tumor adjacent normal tissue samples using qRT-PCR.RESULTS: Five lncRNAs had proper sensitivity and specificity and had target genes involved in cancer-related signaling pathways; however, they showed different expression pattern in TCGA data and in vitro.CONCLUSIONS: The results of our study demonstrated that the five-lncRNAs PART1, UCA1, DIRC3, HOTAIR, and HOXA11AS require more investigation to be confirmed as a diagnostic biomarker in gastric cancer.