Nucleic Acid Guided Molecular Tool for In-Vivo Theranostic Applications

Aptamers ◽  
2019 ◽  
pp. 101-122
Author(s):  
Shahnawaz Ahmad Baba ◽  
Ruchi Mutreja ◽  
Arun Beniwal ◽  
Shubham Jain ◽  
Ekta Yadav ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Molecular Tool ◽  
Theranostic Applications

A GATA3 Targeting Nucleic Acid Nanocapsule for In Vivo Gene Regulation in Asthma

ACS Nano ◽  
2021 ◽  
Author(s):  
Tyler D. Gavitt ◽  
Alyssa K. Hartmann ◽  
Shraddha S. Sawant ◽  
Arlind B. Mara ◽  
Steven M. Szczepanek ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Nucleic Acid

scholarly journals Nanoparticle Delivered Anti-miR-141-3p for Stroke Therapy

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1011
Author(s):  
Karishma Dhuri ◽  
Rutesh N. Vyas ◽  
Leslie Blumenfeld ◽  
Rajkumar Verma ◽  
Raman Bahal
Keyword(s):  
Ischemic Stroke ◽  
Nucleic Acid ◽  
Double Emulsion ◽  
Artery Occlusion ◽  
Brain Parenchyma ◽  
Confocal Imaging ◽  
In Vivo Studies ◽  
Stroke Therapy ◽  
Systemic Delivery

Ischemic stroke and factors modifying ischemic stroke responses, such as social isolation, contribute to long-term disability worldwide. Several studies demonstrated that the aberrant levels of microRNAs contribute to ischemic stroke injury. In prior studies, we established that miR-141-3p increases after ischemic stroke and post-stroke isolation. Herein, we explored two different anti-miR oligonucleotides; peptide nucleic acid (PNAs) and phosphorothioates (PS) for ischemic stroke therapy. We used US FDA approved biocompatible poly (lactic-co-glycolic acid) (PLGA)-based nanoparticle formulations for delivery. The PNA and PS anti-miRs were encapsulated in PLGA nanoparticles by double emulsion solvent evaporation technique. All the formulated nanoparticles showed uniform morphology, size, distribution, and surface charge density. Nanoparticles also exhibited a controlled nucleic acid release profile for 48 h. Further, we performed in vivo studies in the mouse model of ischemic stroke. Ischemic stroke was induced by transient (60 min) occlusion of middle cerebral artery occlusion followed by a reperfusion for 48 or 72 h. We assessed the blood-brain barrier permeability of PLGA NPs containing fluorophore (TAMRA) anti-miR probe after systemic delivery. Confocal imaging shows uptake of fluorophore tagged anti-miR in the brain parenchyma. Next, we evaluated the therapeutic efficacy after systemic delivery of nanoparticles containing PNA and PS anti-miR-141-3p in mice after stroke. Post-treatment differentially reduced both miR-141-3p levels in brain tissue and infarct injury. We noted PNA-based anti-miR showed superior efficacy compared to PS-based anti-miR. Herein, we successfully established that nanoparticles encapsulating PNA or PS-based anti-miRs-141-3p probes could be used as a potential treatment for ischemic stroke.

Biological fate of butylated hydroxytoluene (BHT)-Binding of BHT to nucleic acid in vivo

1980 ◽  
Vol 29 (9) ◽  
pp. 1304-1306 ◽  
Author(s):  
Nakagawa Yoshio ◽  
Hiraga Kogo ◽  
Suga Tetsuya
Keyword(s):  
Nucleic Acid ◽  
Butylated Hydroxytoluene ◽  
Biological Fate

scholarly journals Spontaneous cellular uptake of exogenous messenger RNA in vivo is nucleic acid-specific, saturable and ion dependent

Gene Therapy ◽  
2007 ◽  
Vol 14 (15) ◽  
pp. 1175-1180 ◽  
Author(s):  
J Probst ◽  
B Weide ◽  
B Scheel ◽  
B J Pichler ◽  
I Hoerr ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Cellular Uptake ◽  
Messenger Rna

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...

scholarly journals Antiviral effect of hepatitis B virus S/C gene loci antisense locked nucleic acid on transgenic mice in vivo

2015 ◽  
Vol 14 (3) ◽  
pp. 10087-10095 ◽  
Author(s):  
Y.B. Deng ◽  
H.J. Qin ◽  
Y.H. Luo ◽  
Z.R. Liang ◽  
J.J. Zou
Keyword(s):  
Hepatitis B Virus ◽  
Nucleic Acid ◽  
Hepatitis B ◽  
Transgenic Mice ◽  
Antiviral Effect ◽  
Locked Nucleic Acid ◽  
B Virus

scholarly journals Aptamer Applications in Neuroscience

2021 ◽  
Author(s):  
Meric Ozturk ◽  
Marit Nilsen-Hamilton ◽  
Muslum Ilgu
Keyword(s):  
Multiple Sclerosis ◽  
Amyotrophic Lateral Sclerosis ◽  
Nucleic Acid ◽  
Brain Tumors ◽  
Neurological Disorders ◽  
Neurological Diseases ◽  
Treatment Options ◽  
Health Community ◽  
Theranostic Applications ◽  
Lateral Sclerosis

Being the predominant cause of disability, neurological diseases have received much attention from the global health community. Over a billion people suffer from one of the following neurological disorders: dementia, epilepsy, stroke, migraine, meningitis, Alzheimer's disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, Huntington’s disease, prion dis-ease, or brain tumors. Diagnosis and treatment options are limited for many of these diseases. Aptamers, being small and non-immunogenic nucleic acid molecules that are easy to chemically modify, offer potential diagnostic and theranostic applications to meet these needs. This review covers pioneer studies to apply aptamers, which show promise for future diagnostics and treatments of neurological disorders that pose increasingly dire worldwide health challenges.

scholarly journals Humanization, Radiolabeling and Biodistribution Studies of an IgG1-Type Antibody Targeting Uncomplexed PSA for Theranostic Applications

2021 ◽  
Vol 14 (12) ◽  
pp. 1251
Author(s):  
Joanna Strand ◽  
Kjell Sjöström ◽  
Urpo J. Lamminmaki ◽  
Oskar Vilhelmsson Timmermand ◽  
Sven-Erik Strand ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Specific Binding ◽  
Hek293 Cells ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Biodistribution Studies ◽  
Indium 111 ◽  
Hormone Refractory ◽  
Theranostic Applications

Metastatic castration-resistant prostate cancer is today incurable. Conventional imaging methods have limited detection, affecting their ability to give an accurate outcome prognosis, and current therapies for metastatic prostate cancer are insufficient. This inevitably leads to patients relapsing with castration-resistant prostate cancer. Targeting prostate-specific antigens whose expression is closely linked to the activity in the androgen receptor pathway, and thus the pathogenesis of prostate cancer, is a possible way to increase specificity and reduce off-target effects. We have humanized and evaluated radioimmunoconjugates of a previously murine antibody, m5A10, targeting PSA intended for theranostics of hormone-refractory prostate cancer. The humanized antibody h5A10 was expressed in mammalian HEK293 cells transfected with the nucleotide sequences for the heavy and light chains of the antibody. Cell culture medium was filtered and purified by Protein G chromatography, and the buffer was changed to PBS pH 7.4 by dialysis. Murine and humanized 5A10 were conjugated with p-SCN-Bn-CHX-A”-DTPA. Surface plasmon resonance was used to characterize the binding to PSA of the immunoconjugates. Immunoconjugates were labeled with either indium-111 or lutetium-177. Biodistribution studies of murine and humanized 5A10 were performed in mice with LNCaP xenografts. 5A10 was successfully humanized, and in vivo targeting showed specific binding in xenografts. The results thus give an excellent platform for further theranostic development of humanized 5A10 for clinical applications.

scholarly journals Molecularly self-assembled nucleic acid nanoparticles for targeted in vivo siRNA delivery

2012 ◽  
Vol 7 (6) ◽  
pp. 389-393 ◽  
Author(s):  
Hyukjin Lee ◽  
Abigail K. R. Lytton-Jean ◽  
Yi Chen ◽  
Kevin T. Love ◽  
Angela I. Park ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Sirna Delivery ◽  
Self Assembled
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