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Selective Targeting to Glioma with Nucleic Acid Aptamers.

ABSTRACT: Malignant glioma is characterised by a rapid growth rate and high capacity for invasive infiltration to surrounding brain tissue; hence, diagnosis and treatment is difficult and patient survival is poor. Aptamers contribute a promising and unique technology for the in vitro imaging of live cells and tissues, with a potentially bright future in clinical diagnostics and therapeutics for malignant glioma. The binding selectivity, uptake capacity and binding target of two DNA aptamers, SA43 and SA44, were investigated in glioma cells and patient tissues. The binding assay showed that SA43 and SA44 bound with strong affinity (Kd, 21.56 ± 4.60 nM and Kd, 21.11 ± 3.30 nM respectively) to the target U87MG cells. Quantitative analysis by flow cytometry showed that the aptamers were able to actively internalise in U87MG and 1321N1 glioma cells compared to the non-cancerous and non-glioma cell types. Confocal microscopy confirmed staining in the cytoplasm, and co-localisation studies with endoplasmic reticulum, Golgi apparatus and lysosomal markers suggested internalisation and compartmentalisation within the endomembrane system. Both aptamers selectively bound to Ku 70 and Ku 80 DNA repair proteins as determined by aptoprecipitation (AP) followed by mass spectrometry analysis and confirmation by Western blot. In addition, aptohistochemical (AHC) staining on paraffin embedded, formalin fixed patient tissues revealed that the binding selectivity was significantly higher for SA43 aptamer in glioma tissues (grade I, II, III and IV) compared to the non-cancerous tissues, whereas SA44 did not show selectivity towards glioma tissues. The results indicate that SA43 aptamer can differentiate between glioma and non-cancerous cells and tissues and therefore, shows promise for histological diagnosis of glioma.

SUBMITTER: Aptekar S

PROVIDER: S-EPMC4529171 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Selective Targeting to Glioma with Nucleic Acid Aptamers.

Aptekar Shraddha S Arora Mohit M Lawrence Clare Louise CL Lea Robert William RW Ashton Katherine K Dawson Tim T Alder Jane Elizabeth JE Shaw Lisa L

PloS one 20150807 8

Malignant glioma is characterised by a rapid growth rate and high capacity for invasive infiltration to surrounding brain tissue; hence, diagnosis and treatment is difficult and patient survival is poor. Aptamers contribute a promising and unique technology for the in vitro imaging of live cells and tissues, with a potentially bright future in clinical diagnostics and therapeutics for malignant glioma. The binding selectivity, uptake capacity and binding target of two DNA aptamers, SA43 and SA44 ...[more]

PMID: 26252900

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Project description:The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently creating a global health emergency. This crisis is driving a worldwide effort to develop effective vaccines, prophylactics, and therapeutics. Nucleic acid (NA)-based treatments hold great potential to combat outbreaks of coronaviruses (CoVs) due to their rapid development, high target specificity, and the capacity to increase druggability. Here, we review key anti-CoV NA-based technologies, including antisense oligonucleotides (ASOs), siRNAs, RNA-targeting clustered regularly interspaced short palindromic repeats-CRISPR-associated protein (CRISPR-Cas), and mRNA vaccines, and discuss improved delivery methods and combination therapies with other antiviral drugs. Highlights Nucleic-acid based therapies are worth developing against coronavirus (CoV) outbreaks because of their high specificity and rapid development. Several key therapeutic nucleic acid (TNA) strategies, including antisense oligonucleotides (ASOs), siRNA, and RNA-targeting clustered regularly interspaced short palindromic repeats-CRISPR-associated protein (CRISPR-Cas) technologies targeting the viral genome are potentially applicable to combat CoVs. mRNA vaccines are attractive candidates to control CoV outbreaks with rapid/easy manufacturing, high potency, and safety. Optimal therapeutic cocktails comprising different TNAs or TNAs with other antiviral agents could act on multiple targets simultaneously, thereby enhancing antiviral effects and reducing risk of drug resistance. Lipid-ASO (LASO) nanomicelles enable cellular self-uptake and can be conjugated with antiviral molecules, providing promising anti-CoV combinational therapeutics that can be delivered directly to the lungs by aerosol. Advancement in chemical modifications and delivery vehicles remarkably enhance stability and pharmacokinetic profile of TNAs, facilitating clinical application of numerous TNAs; however, more studies on optimal chemical manufacturing and delivery methods improving safety and efficiency for TNAs are needed.

Dataset Information

Selective Targeting to Glioma with Nucleic Acid Aptamers.

Publications

Selective Targeting to Glioma with Nucleic Acid Aptamers.

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