CRISPR-based RNA editing: diagnostic applications and therapeutic options

Gulei, Diana; Ráduly, Lajos; Berindan‐Neagoe, Ioana; Calin, George A.

doi:10.1080/14737159.2019.1568242

Cited by 14 publications

(7 citation statements)

References 48 publications

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“…To regain the function of a lncRNA that is lost or downregulated in a myeloid malignancy, the simplest method is to supply with synthetic lncRNA molecules with same function (141). This could be achieved with a non-coding RNA mimic or with its expression vectors (142, 143). When transfected into cells, lncRNA mimics could be processed into a single-strand RNA molecule to target coding genes similar to the endogenous lncRNA, but viable experimental data has yet to be published.…”

Section: Long Non-coding Rnas In Myeloid Malignancies—analysis Of Prementioning

confidence: 99%

Long Non-coding RNAs in Myeloid Malignancies

et al. 2019

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Acute myeloid leukemia (AML) represents 80% of adult leukemias and 15–20% of childhood leukemias. AML are characterized by the presence of 20% blasts or more in the bone marrow, or defining cytogenetic abnormalities. Laboratory diagnoses of myelodysplastic syndromes (MDS) depend on morphological changes based on dysplasia in peripheral blood and bone marrow, including peripheral blood smears, bone marrow aspirate smears, and bone marrow biopsies. As leukemic cells are not functional, the patient develops anemia, neutropenia, and thrombocytopenia, leading to fatigue, recurrent infections, and hemorrhage. The genetic background and associated mutations in AML blasts determine the clinical course of the disease. Over the last decade, non-coding RNAs transcripts that do not codify for proteins but play a role in regulation of functions have been shown to have multiple applications in the diagnosis, prognosis and therapeutic approach of various types of cancers, including myeloid malignancies. After a comprehensive review of current literature, we found reports of multiple long non-coding RNAs (lncRNAs) that can differentiate between AML types and how their exogenous modulation can dramatically change the behavior of AML cells. These lncRNAs include: H19, LINC00877, RP11-84C10, CRINDE, RP11848P1.3, ZNF667-AS1, AC111000.4-202, SFMBT2, LINC02082-201, MEG3, AC009495.2, PVT1, HOTTIP, SNHG5, and CCAT1. In addition, by performing an analysis on available AML data in The Cancer Genome Atlas (TCGA), we found 10 lncRNAs with significantly differential expression between patients in favorable, intermediate/normal, or poor cytogenetic risk categories. These are: DANCR, PRDM16-DT, SNHG6, OIP5-AS1, SNHG16, JPX, FTX, KCNQ1OT1, TP73-AS1, and GAS5. The identification of a molecular signature based on lncRNAs has the potential for have deep clinical significance, as it could potentially help better define the evolution from low-grade MDS to high-grade MDS to AML, changing the course of therapy. This would allow clinicians to provide a more personalized, patient-tailored therapeutic approach, moving from transfusion-based therapy, as is the case for low-grade MDS, to the introduction of azacytidine-based chemotherapy or allogeneic stem cell transplantation, which is the current treatment for high-grade MDS.

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Section: Long Non-coding Rnas In Myeloid Malignancies—analysis Of Prementioning

confidence: 99%

Long Non-coding RNAs in Myeloid Malignancies

et al. 2019

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“…Another important determinant in the development of the malignant phenotype in NSCLCs is represented by the noncoding part of the genome (8). Over the last two decades, microRNAs (miRNAs) gained the attention of the medical researchers, as they were proved to be important players in cancer development (9)(10)(11). MiRNAs represent short RNAs that do not undergo the translation into proteins, but regulate the expression of many protein coding genes, by complementary binding (12).…”

Section: Introductionmentioning

confidence: 99%

The Clinical Utility of miR-21 and let-7 in Non-small Cell Lung Cancer (NSCLC). A Systematic Review and Meta-Analysis

et al. 2020

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Non-small cell lung cancer (NSCLC) remains a problem worldwide due to its rapid progression and low rate of response to treatment. The heterogeneity of these tumors observed in histopathology exam but also in the mutational status and gene expression pattern makes this malignancy difficult to treat in clinic. The present study investigated the effect of miR-21 and let-7 family members as prognostic biomarkers in NSCLC patients based on the results published in different studies regarding this subject until March 2019. The analysis revealed that these two transcripts are steady biomarkers for prediction of patient outcome or survival. Upregulated expression of miR-21 is associated with poor outcome of patients with NSCLC [HR = 1.87, 95% CI = (1.41, 2.47), p < 0.001]. The analysis regarding let-7 family, specifically let-7a/b/e/f, revealed that downregulated expression of these transcripts predicts poor outcome for NSCLC patients [HR = 2.61, 95% CI = (1.58, 4.30), p < 0.001]. Besides, the reliability of these microRNAs is reflected in the fact that their prognostic significance is constant given the different sample types (tissue, FFPE tissue, serum, serum/plasma or exosomes) used in the selected studies.

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“…Therefore, the nucleic acid-based tests are more useful over antibody-based tests to counter the spread of a virus. Therefore, point-of-care and rapid testing fights the spread of highly contagious viruses, as it allows infected individuals to be rapidly identified, so they can be contact-traced and isolated (Table 1 ) [ 11 , 26 ].…”

Section: Pros and Cons Of Crispr-based Diagnosis Systemsmentioning

confidence: 99%

“…The disadvantages associated with current diagnostic strategies such as serological tests and nucleic acid-based tests, led the researchers to develop CRISPR-based techniques DETECTR and SHERLOCK assays [ 13 , 25 ] which are distinguished by targeting DNA and RNA, respectively. The two CRISPR-based strategies meet these criteria in addition to offering unique multiplexing abilities [ 1 , 26 ]. Particularly, the CRISPR-based DETECTR assay is as accurate as qRT–PCR but is a more rapid approach as well.…”

Section: Pros and Cons Of Crispr-based Diagnosis Systemsmentioning

confidence: 99%

CRISPR-Based Diagnosis of Infectious and Noninfectious Diseases

et al. 2020

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Interest in CRISPR technology, an instrumental component of prokaryotic adaptive immunity which enables prokaryotes to detect any foreign DNA and then destroy it, has gained popularity among members of the scientific community. This is due to CRISPR’s remarkable gene editing and cleaving abilities. While the application of CRISPR in human genome editing and diagnosis needs to be researched more fully, and any potential side effects or ambiguities resolved, CRISPR has already shown its capacity in an astonishing variety of applications related to genome editing and genetic engineering. One of its most currently relevant applications is in diagnosis of infectious and non-infectious diseases. Since its initial discovery, 6 types and 22 subtypes of CRISPR systems have been discovered and explored. Diagnostic CRISPR systems are most often derived from types II, V, and VI. Different types of CRISPR-Cas systems which have been identified in different microorganisms can target DNA (e.g. Cas9 and Cas12 enzymes) or RNA (e.g. Cas13 enzyme). Viral, bacterial, and non-infectious diseases such as cancer can all be diagnosed using the cleavage activity of CRISPR enzymes from the aforementioned types. Diagnostic tests using Cas12 and Cas13 enzymes have already been developed for detection of the emerging SARS-CoV-2 virus. Additionally, CRISPR diagnostic tests can be performed using simple reagents and paper-based lateral flow assays, which can potentially reduce laboratory and patient costs significantly. In this review, the classification of CRISPR-Cas systems as well as the basis of the CRISPR/Cas mechanisms of action will be presented. The application of these systems in medical diagnostics with emphasis on the diagnosis of COVID-19 will be discussed.

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CRISPR-based RNA editing: diagnostic applications and therapeutic options

Cited by 14 publications

References 48 publications

Long Non-coding RNAs in Myeloid Malignancies

Long Non-coding RNAs in Myeloid Malignancies

The Clinical Utility of miR-21 and let-7 in Non-small Cell Lung Cancer (NSCLC). A Systematic Review and Meta-Analysis

CRISPR-Based Diagnosis of Infectious and Noninfectious Diseases

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