The importance of circular RNAs (circRNAs) in pathological processes like cancer is evident. Among the circRNAs, recent studies have brought circPVT1 under focus as the most potent oncogenic non-coding RNA. Recent studies on various aspects of circPVT1, including its biogenesis, molecular alteration and its probable role in oncogenesis, have been conducted for research and clinical interest. In this review, a first attempt has been made to summarise the available data on circPVT1 from PubMed and other relevant databases with special emphasis on its role in development, progression and prognosis of various malignant conditions. CircPVT1 is derived from the same genetic locus encoding for long non-coding RNA lncPVT1; however, existing literature suggested circPVT1 and lncPVT1 are transcripted independently by different promoters. The interaction between circRNA and microRNA has been highlighted in majority of the few malignancies in which circPVT1 was studied. Besides its importance in diagnostic and prognostic procedures, circPVT1 seemed to have huge therapeutic potential as evident from differential drug response of cancer cell line as well as primary tumors depending on expression level of the candidate. circPVT1 in cancer therapeutics might be promising as a biomarker to make the existing treatment protocol more effective and also as potential target for designing novel therapeutic intervention.
<p>SARS-CoV-2 uses RBD of Spike (S) protein to attach with human cell via ACE2 receptor, followed by protease priming at S1/S2 site resulted in host cell entry and pathogenesis. In this context, we focused our aim in studying natural mutations harboring in Spike protein of SARS-CoV-2. We have analyzed 420 COVID-19 cases. G476S and V483G mutation are observed which lies in the RBD region where as the prevalent D614G mutation is observed in the vicinity of S1/S2 site. Interestingly MD simulation supports strong favorable interaction of ACE2 with RBD region containing V483A mutation as compared to G476S and reference wild Wuhan S protein. Radius of gyration analysis also showed high degree of compactness in V483A. The landscape plot and Gibbs free energy also support our findings. Overall, our study indicates that V483G in the RBD region can enhance its binding with the human ACE2 receptor. Interestingly D614G mutation in vicinity of S1/S2 region introduced a new cleavage site specific for a serine protease elastase that is anticipated to broaden the virus host cell tropism. Hence, both V483A and D614G mutations led to enhanced and broaden the virus host cell entry and transmission of the disease. Further epitope mapping analysis revealed G476S and D614G mutations as antigenic determinants and thus these mutations are important while designing a therapeutics vaccine or chimeric antibody. This finding will help in further understanding the role of such arising mutations in modulating immunogenicity, viral tropism and pathogenesis of the disease, which in lieu will help in designing vaccine more precisely to mitigate pandemic COVID-19. </p> <p> </p>
An aptamer is a short sequence of synthetic oligonucleotides which bind to their cognate target, specifically while maintaining similar or higher sensitivity compared to an antibody. The in-vitro selection of an aptamer, applying a conjoining approach of chemistry and molecular biology, is referred as Systematic Evolution of Ligands by Exponential enrichment (SELEX). These initial products of SELEX are further modified chemically in an attempt to make them stable in biofluid, avoiding nuclease digestion and renal clearance. While the modification is incorporated, enough care should be taken to maintain its sensitivity and specificity. These modifications and several improvisations have widened the window frame of aptamer applications that are currently not only restricted to in-vitro systems, but have also been used in molecular imaging for disease pathology and treatment. In the food industry, it has been used as sensor for detection of different diseases and fungal infections. In this review, we have discussed a brief history of its journey, along with applications where its role as a therapeutic plus diagnostic (theranostic) tool has been demonstrated. We have also highlighted the potential aptamer-mediated strategies for molecular targeting of COVID-19. Finally, the review focused on its future prospective in immunotherapy, as well as in identification of novel biomarkers in stem cells and also in single cell proteomics (scProteomics) to study intra or inter-tumor heterogeneity at the protein level. Small size, chemical synthesis, low batch variation, cost effectiveness, long shelf life and low immunogenicity provide advantages to the aptamer over the antibody. These physical and chemical properties of aptamers render them as a strong biomedical tool for theranostic purposes over the existing ones. The significance of aptamers in human health was the key finding of this review.
Aptamer is short sequence of synthetic oligonucleotides which bind to their cognate target specifically while maintaining similar or higher sensitivity as antibody. Small size, chemical synthesis, low batch variation, cost effectiveness, long shelf life and above all low immunogenicity provide advantages over antibody. The in-vitro selection of aptamer applying a conjoining approach of chemistry and molecular biology is referred as Systematic Evolution of Ligands by Exponential enrichment (SELEX). These initial products of SELEX are considered as first generation aptamers, further modified chemically in an attempt to make it stable in biofluid avoiding nuclease digestion and renal clearance. These types of aptamers are called second generation aptamers. While modification is incorporated, enough care should be taken to maintain its sensitivity and specificity. These modifications and several improvisations have widened the window frame of aptamer application that is currently not only restricted to in-vitro system, but have been used in molecular imaging for disease pathology and treatment. In food industry it is used as sensor for detection of different diseases or fungal infections. In this review we have discussed a brief history of its journey, process of synthesis, different types of modifications to improve its characters. We have also focused on its applications and highlighted its role as therapeutic plus diagnostic; theranostic tools. Finally, the review is concluded with a brief discussion on future prospective in immunotherapy, as well as in identification of novel biomarkers in stem cell, and also in single cell proteomics (scProteomics) to study intra or intertumor heterogeneity at protein level.
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