1,4-Butanediol diglycidyl ether (BDE)-crosslinked PEI-g-imidazole nanoparticles as nucleic acid-carriers in vitro and in vivo

2011 ◽  
Vol 7 (6) ◽  
pp. 2055 ◽  
Author(s):  
Ritu Goyal ◽  
Ruby Bansal ◽  
Shilpa Tyagi ◽  
Yogeshwer Shukla ◽  
Pradeep Kumar ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Diglycidyl Ether

IMMU-53. STING-ING GLIOBLASTOMA WITH SPHERICAL NUCLEIC ACIDS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi104-vi105
Author(s):  
Akanksha Mahajan ◽  
Lisa Hurley ◽  
Serena Tommasini-Ghelfi ◽  
Corey Dussold ◽  
Alexander Stegh ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
High Surface ◽  
Biological Properties ◽  
Innate Immune ◽  
Limiting Factors ◽  
Nucleic Acid Delivery ◽  
Sting Pathway ◽  
Spherical Nucleic Acids

Abstract The Stimulator of Interferon Genes (STING) pathway represents a major innate immune sensing mechanism for tumor-derived DNA. Modified cyclic dinucleotides (CDNs) that mimic the endogenous STING ligand cGAMP are currently being explored in patients with solid tumors that are amenable to intratumoral delivery. Inadequate bioavailability and insufficient lipophilicity are limiting factors for clinical CDN development, in particular when consideration is given to systemic administration approaches. We have shown that the formulation of oligonucleotides into Spherical Nucleic Acid (SNA) nanostructures, i.e.,the presentation of oligonucleotides at high density on the surface of nanoparticle cores, lead to biochemical and biological properties that are radically different from those of linear oligonucleotides. First-generation brain-penetrant siRNA-based SNAs (NCT03020017, recurrent GBM) have recently completed early clinical trials. Here, we report the development of a STING-agonistic immunotherapy by targeting cGAS, the sensor of cytosolic dsDNA upstream of STING, with SNAs presenting dsDNA at high surface density. The strategy of using SNAs exploits the ability of cGAS to raise STING responses by delivering dsDNA and inducing the catalytic production of endogenous CDNs. SNA nanostructures carrying a 45bp IFN-simulating dsDNA oligonucleotide, the most commonly used and widely characterized cGAS activator, potently activated the cGAS-STING pathway in vitro and in vivo. In a poorly immunogenic and highly aggressive syngeneic mouse glioma model, in which tumours were well-established, only one dose of intranasal treatment with STING-SNAs decelerated tumour growth, improved survival and importantly, was well-tolerated. Our use of SNAs addresses the challenges of nucleic acid delivery to intracranial tumor sites via intranasal route, exploits the binding of dsDNA molecules on the SNA surface to enhance the formation of a dimeric cGAS:DNA complex and establishes cGAS-agonistic SNAs as a novel class of immune-stimulatory modalities for triggering innate immune responses against tumor.

Framework nucleic acid programmed combinatorial delivery nanocarriers for parallel and multiplexed analysis

2021 ◽  
Author(s):  
Yinghui Feng ◽  
Qi Liu ◽  
Miao Chen ◽  
Xinyi Zhao ◽  
Lumin Wang ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Multiplexed Analysis

Herein we report a framework nucleic acid programmed strategy to develop nanocarriers to precisely and independently package multiple homo- and heterogeneous cargos in vitro and in vivo, thereby enabling multiplexed...

Regulation der Chlorophyllbiosynthese. Lidit- und entwicklungsbedingte Aktivitätsänderungen von vier aufeinander folgenden Enzymen der Porphyrin- und Chlorophyllbiosynthesekette / Regulation of Chlorophyll Biosynthesis. Changes in Activity of Four Consecutive Enzymes in the Porphyrin and Chlorophyll Biosynthesis Chain during Development and Illumination

1973 ◽  
Vol 28 (1-2) ◽  
pp. 45-58 ◽  
Author(s):  
Hansjörg A. W. Schneider
Keyword(s):  
Nucleic Acid ◽  
Chlorophyll Biosynthesis ◽  
Acid Synthesis ◽  
Chlorophyll Synthesis ◽  
The Other ◽  
Tissue Cultures ◽  
Leaf Tissues ◽  
Porphyrin Synthesis

The activities of enzymes related with chlorophyll and porphyrin synthesis have been examined during development and greening of young corn leaves. The enzymes succinyl-CoA-synthetase (SCoAS), δ-amino-levulinate synthetase (ALAS), δ-amino-levulinate dehydratase (ALAD) and the enzymes involved in porphobilinogenase (PBGA) were under investigaton. When leaves are illuminated and chlorophyll synthesis begins the activity of ALAD is not influenced. The activity of PBGA and SCoAS are slightly higher than in darkness, but the changes are below the range affecting chlorophyll biosynthesis. ALA, however, is only synthetized in the light. Synthesis ceases immediately when illuminiation ist stopped, indicating'that in darkness ALAS is not active. On the other hand ALAS is active in dark grown roots, tubers and other non-leaf tissues. Feeding the plant with succinate, glycine or α-keto-glutarate has no effect on chlorophyll synthesis, but the amount of ALA is reduced, whereas sucrose promotes its accumulation. The results are discussed with completely antitethaal results obtained with tissue cultures of tobacco and are integrated into a scheme which excludes the contrariety of hypotheses deduced from experi- ments with inhibitors of protein and nucleic acid synthesis. It is suggested that the varying results are caused by the action of light on different stages in differentiation of plastids and cells. In contrast to the enzymes SCoAS, ALAD and PBGA whose activities were determined in vitro, ALAS was assayed in vivo by means of the accumulation of (5-amino-levulinate (ALA) after blocking the enzyme ALAD by levulinate (LA). Optimum accumulation is observed when the concentration is about 2 · 10-2 м. LA is not converted to ALA in appreciable amounts. This could be proved by feeding the plants with 14C-LA which was prepared from uniformly labeled 14C-fructose.

scholarly journals Crucial Role of Nucleic Acid Sensing via Endosomal Toll-Like Receptors for the Defense of Streptococcus pyogenes in vitro and in vivo

2019 ◽  
Vol 10 ◽  
Author(s):  
Anna Hafner ◽  
Ulrike Kolbe ◽  
Isabel Freund ◽  
Virginia Castiglia ◽  
Pavel Kovarik ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Streptococcus Pyogenes ◽  
Crucial Role ◽  
Toll Like Receptors

scholarly journals HA-based dermal filler: downstream process comparison, impurity quantitation by validated HPLC-MS analysis, and in vivo residence time study

2019 ◽  
Vol 17 (3) ◽  
pp. 228080001986707 ◽  
Author(s):  
Cristian Guarise ◽  
Carlo Barbera ◽  
Mauro Pavan ◽  
Susi Panfilo ◽  
Riccardo Beninatto ◽  
...  
Keyword(s):  
Residence Time ◽  
Rabbit Model ◽  
Diglycidyl Ether ◽  
In Vitro Cytotoxicity ◽  
Dermal Filler ◽  
Dermal Fillers ◽  
Process Comparison ◽  
Hygroscopic Properties

The success of hyaluronic acid (HA)-based dermal fillers, with more than 2 million minimally invasive procedures conducted in 2016 in the US alone, is due to their hygroscopic properties of biocompatibility and reversibility. The type and density of HA cross-linkage, as well as the manufacturing technology, may influence not only the in vivo persistence but also the safety profile of dermal fillers. 1,4-Butanediol diglycidyl ether (BDDE) is the cross-linker used in most market-leading HA fillers; 1,4-butanediol di-(propan-2,3-diolyl) ether (BDPE) is the major impurity obtained from the HA–BDDE cross-linking (HBC) process. In this work, a new process to obtain high purity HBC fillers was developed. A new HPLC-MS method was validated for the quantification of BDPE content in HBC dermal fillers. In vitro cytotoxicity of BDPE was evaluated in fibroblasts (IC50 = 0.48 mg/mL). The viscoelasticity was monitored during the shelf-life of the HBC-10% hydrogel and was correlated with in vitro hyaluronidase resistance and in vivo residence time in a rabbit model. This analysis showed that elasticity is the best parameter to predict the in vivo residence time. Finally, a series of parameters were investigated in certain marketed dermal fillers and were compared with the results of the HBC-10% hydrogel.

scholarly journals A Perspective on Re-Detectable Positive SARS-CoV-2 Nucleic Acid Results in Recovered COVID-19 Patients

2020 ◽  
pp. 1-5
Author(s):  
Yanfei He ◽  
Yu-Chao Dong
Keyword(s):  
Nucleic Acid ◽  
Animal Experiments ◽  
Patient Discharge ◽  
Clinical Work ◽  
Igg Antibody ◽  
Viral Virulence ◽  
And Control ◽  
Nucleic Acid Tests

ABSTRACT Objectives: There have been reports on re-detectable positive nucleic acid tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in recovered coronavirus disease (COVID-19) patients. In this study, we look at the clinical characteristics, possible causes, pathogenesis, and infectivity of re-detectable positive patients and provide up-to-date information to public health policy planners and clinicians. Methods: By consulting the latest research data and related progress data of re-detectable positive patients, this study addresses the implications that this special group brings to clinical work and disease prevention and control. Results: We discuss in detail the phenomenon of re-detectable positive nucleic acid tests for recovered patients. There are many possible causes of a re-detectable positive, but there is no 1 factor that can fully explain this phenomenon. Conclusions: It can’t be completely ruled out that the re-detectable positive patients are infectious. We should be alert to these re-detectable positive patients becoming chronic virus carriers, and virus serological IgM and IgG antibody tests should be added before patient discharge. It is urgent to find a more powerful evidence-based and virological basis for the integrity of viral ribonucleic acid and the variation of viral virulence with time through cell experiments in vitro and animal experiments in vivo.

Nucleic Acid AptamersFrom Selection in Vitro to Applications in Vivo

2000 ◽  
Vol 33 (9) ◽  
pp. 591-599 ◽  
Author(s):  
Michael Famulok ◽  
Günter Mayer ◽  
Michael Blind
Keyword(s):  
Nucleic Acid
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