scholarly journals The Challenges and Strategies of Antisense Oligonucleotide Drug Delivery

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 433
Author(s):  
Maria Gagliardi ◽  
Ana Tari Ashizawa
Keyword(s):  
Growth Factor Receptor ◽  
Hematologic Malignancies ◽  
Therapeutic Modality ◽  
Antisense Oligodeoxynucleotide ◽  
Full Potential ◽  
Preclinical Research ◽  
Wide Range ◽  
Disease Associated Genes ◽  
Preclinical And Clinical Studies ◽  
Growth Factor Receptor Bound

Antisense oligonucleotides (ASOs) are used to selectively inhibit the translation of disease-associated genes via Ribonuclease H (RNaseH)-mediated cleavage or steric hindrance. They are being developed as a novel and promising class of drugs targeting a wide range of diseases. Despite the great potential and numerous ASO drugs in preclinical research and clinical trials, there are many limitations to this technology. In this review we will focus on the challenges of ASO delivery and the strategies adopted to improve their stability in the bloodstream, delivery to target sites, and cellular uptake. Focusing on liposomal delivery, we will specifically describe liposome-incorporated growth factor receptor-bound protein-2 (Grb2) antisense oligodeoxynucleotide BP1001. BP1001 is unique because it is uncharged and is essentially non-toxic, as demonstrated in preclinical and clinical studies. Additionally, its enhanced biodistribution makes it an attractive therapeutic modality for hematologic malignancies as well as solid tumors. A detailed understanding of the obstacles that ASOs face prior to reaching their targets and continued advances in methods to overcome them will allow us to harness ASOs’ full potential in precision medicine.

Recent Applications of High Resolution Electron Microscopy to Crystalline Arrays of Virus Particles

1978 ◽  
Vol 36 (3) ◽  
pp. 470-482 ◽  
Author(s):  
R.W. Horne
Keyword(s):  
Electron Microscopy ◽  
Image Processing ◽  
Analytical Techniques ◽  
Staining Technique ◽  
High Resolution Electron Microscopy ◽  
Optical Diffraction ◽  
Full Potential ◽  
Virus Particles ◽  
Resolution Electron ◽  
Wide Range

The technique of surrounding virus particles with a neutralised electron dense stain was described at the Fourth International Congress on Electron Microscopy, Berlin 1958 (see Home & Brenner, 1960, p. 625). For many years the negative staining technique in one form or another, has been applied to a wide range of biological materials. However, the full potential of the method has only recently been explored following the development and applications of optical diffraction and computer image analytical techniques to electron micrographs (cf. De Hosier & Klug, 1968; Markham 1968; Crowther et al., 1970; Home & Markham, 1973; Klug & Berger, 1974; Crowther & Klug, 1975). These image processing procedures have allowed a more precise and quantitative approach to be made concerning the interpretation, measurement and reconstruction of repeating features in certain biological systems.

Occurrence of GRB10 (+11275G > A) polymorphism in Hungarian population and its relationship to glucose metabolism

2009 ◽  
Vol 150 (40) ◽  
pp. 1845-1851 ◽  
Author(s):  
Márta Vitai ◽  
Barbara Buday ◽  
Enikő Kulcsár ◽  
Botond Literáti-Nagy ◽  
Istvánné Vecsei ◽  
...  
Keyword(s):  
Growth Factor ◽  
Glucose Metabolism ◽  
Growth Factor Receptor ◽  
Hungarian Population ◽  
Growth Factor Receptor Bound

Az előkísérletünk során az egészséges és spontán hipertóniás patkányok között génexpressziós különbségeket találtunk „differencial display” eljárással. Az eltérően expresszált gének között szerepelt a GRB10 gén, amelynek terméke a GRB10 (Growth factor receptor-bound protein) fehérje. A GRB10 protein kötődik az inzulinreceptorokhoz, negatív regulátorproteinként tartják számon és polimorfizmusait összefüggésbe hozták a 2-es típusú diabétesz kialakulásával. Vizsgálatunk során a GRB10 gén +11275G > A(RS 2237457) polimorfizmusát vizsgáltuk magyarországi 2-es típusú cukorbetegek és egészségesek esetében (2DM-es beteg n = 85, egészséges kontroll n = 77). Kerestük az összefüggéseket a genotípus és a hyperinsulinaemiás-normoglykaemiás clamp vizsgálattal mért, a glükózhomeosztázisra jellemző paraméterek között egészséges (n = 88) és glükózintoleráns (IFG n = 15; IGT n = 29 és kezelést nem igénylő 2-es típusú diabéteszes: n = 9) betegek esetében. A hazai populációban nem találtunk szignifikáns különbséget az allélgyakoriság között az egészséges és a 2DM-csoport között (egészséges g vs. a: 62% vs. 38%; 2DM g vs. a: 70% vs. 30%). Az inzulinérzékenységet tükröző glükózfelhasználás nők esetében nem függött a GRB10 gén polimorfizmusától. Férfiak esetében a gg polimorfizmus az OGTT glükózterhelés során fokozott, de az ivGTT-terhelés során azonos mértékű inzulinelválasztással társult. Férfiakban gg allél esetében alacsonyabb az izomtömeg glükózfelhasználása, az egész test és az izomszövet vonatkozásában a glükózeltűnési ráta, és mindkét nemben rosszabb a lipidprofil, alacsonyabb a kisebb denzitású, nagyobb molekulájú LDL-frakciók koncentrációja, nők esetében pedig a HDL-koleszterin-vérszint. A GRB10 génpolimorfizmussal kapcsolatos anyagcsere-eltérések alátámasztják – a „prediabéteszes” időszakban – a génnek az inzulinérzékenységben és inzulinelválasztásban feltételezett szerepét, amely azonban nemhez kötött és csak férfiakban észlelhető. A po. és iv. cukorterhelés alatt mért inzulinelválasztási eltérések alapján felvethető, hogy a GRB10 gén az inkretin jelátvitelben is szerepet játszik.

scholarly journals Are We Paving the Way to Dig Out of the “Pandemic Hole”? A Narrative Review on SARS-CoV-2 Vaccination: From Animal Models to Human Immunization

2021 ◽  
Vol 9 (3) ◽  
pp. 53
Author(s):  
Giuseppe Tardiolo ◽  
Pina Brianti ◽  
Daniela Sapienza ◽  
Pia dell’Utri ◽  
Viviane Di Dio ◽  
...  
Keyword(s):  
Animal Models ◽  
Viral Vector ◽  
Herd Immunity ◽  
Population Level ◽  
Narrative Review ◽  
Therapeutic Interventions ◽  
Preclinical Research ◽  
Inactivated Vaccines ◽  
Preclinical And Clinical Studies ◽  
Social Upheaval

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a new pathogen agent causing the coronavirus infectious disease (COVID-19). This novel virus originated the most challenging pandemic in this century, causing economic and social upheaval internationally. The extreme infectiousness and high mortality rates incentivized the development of vaccines to control this pandemic to prevent further morbidity and mortality. This international scenario led academic scientists, industries, and governments to work and collaborate strongly to make a portfolio of vaccines available at an unprecedented pace. Indeed, the robust collaboration between public systems and private companies led to resolutive actions for accelerating therapeutic interventions and vaccines mechanism. These strategies contributed to rapidly identifying safe and effective vaccines as quickly and efficiently as possible. Preclinical research employed animal models to develop vaccines that induce protective and long-lived immune responses. A spectrum of vaccines is worldwide under investigation in various preclinical and clinical studies to develop both individual protection and safe development of population-level herd immunity. Companies employed and developed different technological approaches for vaccines production, including inactivated vaccines, live-attenuated, non-replicating viral vector vaccines, as well as acid nucleic-based vaccines. In this view, the present narrative review provides an overview of current vaccination strategies, taking into account both preclinical studies and clinical trials in humans. Furthermore, to better understand immunization, animal models on SARS-CoV-2 pathogenesis are also briefly discussed.

scholarly journals Enhanced Bilosomal Properties Resulted in Optimum Pharmacological Effects by Increased Acidification Pathways

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1184
Author(s):  
Armin Mooranian ◽  
Thomas Foster ◽  
Corina M Ionescu ◽  
Daniel Walker ◽  
Melissa Jones ◽  
...  
Keyword(s):  
Bile Acids ◽  
Biological Effects ◽  
Cellular Respiration ◽  
Full Potential ◽  
Protective Effects ◽  
Pharmacological Effects ◽  
Β Cells ◽  
Positive Effects ◽  
Wide Range ◽  
Anti Inflammatory

Introduction: Recent studies in our laboratory have shown that some bile acids, such as chenodeoxycholic acid (CDCA), can exert cellular protective effects when encapsulated with viable β-cells via anti-inflammatory and anti-oxidative stress mechanisms. However, to explore their full potential, formulating such bile acids (that are intrinsically lipophilic) can be challenging, particularly if larger doses are required for optimal pharmacological effects. One promising approach is the development of nano gels. Accordingly, this study aimed to examine biological effects of various concentrations of CDCA using various solubilising nano gel systems on encapsulated β-cells. Methods: Using our established cellular encapsulation system, the Ionic Gelation Vibrational Jet Flow technology, a wide range of CDCA β-cell capsules were produced and examined for morphological, biological, and inflammatory profiles. Results and Conclusion: Capsules’ morphology and topographic characteristics remained similar, regardless of CDCA or nano gel concentrations. The best pharmacological, anti-inflammatory, and cellular respiration, metabolism, and energy production effects were observed at high CDCA and nano gel concentrations, suggesting dose-dependent cellular protective and positive effects of CDCA when incorporated with high loading nano gel.

scholarly journals Mineral Physicochemistry Underlying Feature-Based Extraction of Mineral Abundance and Composition from Shortwave, Mid and Thermal Infrared Reflectance Spectra

Minerals ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 347
Author(s):  
Carsten Laukamp ◽  
Andrew Rodger ◽  
Monica LeGras ◽  
Heta Lampinen ◽  
Ian C. Lau ◽  
...  
Keyword(s):  
Mineral Exploration ◽  
Relevant Information ◽  
Ore Deposits ◽  
Reflectance Spectra ◽  
Full Potential ◽  
Infrared Reflectance ◽  
Vibrational Modes ◽  
Diagnostic Features ◽  
Wide Range ◽  
Mineral Assemblages

Reflectance spectroscopy allows cost-effective and rapid mineral characterisation, addressing mineral exploration and mining challenges. Shortwave (SWIR), mid (MIR) and thermal (TIR) infrared reflectance spectra are collected in a wide range of environments and scales, with instrumentation ranging from spaceborne, airborne, field and drill core sensors to IR microscopy. However, interpretation of reflectance spectra is, due to the abundance of potential vibrational modes in mineral assemblages, non-trivial and requires a thorough understanding of the potential factors contributing to the reflectance spectra. In order to close the gap between understanding mineral-diagnostic absorption features and efficient interpretation of reflectance spectra, an up-to-date overview of major vibrational modes of rock-forming minerals in the SWIR, MIR and TIR is provided. A series of scripts are proposed that allow the extraction of the relative intensity or wavelength position of single absorption and other mineral-diagnostic features. Binary discrimination diagrams can assist in rapidly evaluating mineral assemblages, and relative abundance and chemical composition of key vector minerals, in hydrothermal ore deposits. The aim of this contribution is to make geologically relevant information more easily extractable from reflectance spectra, enabling the mineral resources and geoscience communities to realise the full potential of hyperspectral sensing technologies.

scholarly journals Single-cell mapping of focused ultrasound-transfected brain

Gene Therapy ◽  
2021 ◽  
Author(s):  
A. S. Mathew ◽  
C. M. Gorick ◽  
R. J. Price
Keyword(s):  
Single Cell ◽  
Focused Ultrasound ◽  
Cell Types ◽  
Brain Cell ◽  
Therapeutic Modality ◽  
Full Potential ◽  
Stress Genes ◽  
Multiple Cell ◽  
Differential Gene

AbstractGene delivery via focused ultrasound (FUS) mediated blood-brain barrier (BBB) opening is a disruptive therapeutic modality. Unlocking its full potential will require an understanding of how FUS parameters (e.g., peak-negative pressure (PNP)) affect transfected cell populations. Following plasmid (mRuby) delivery across the BBB with 1 MHz FUS, we used single-cell RNA-sequencing to ascertain that distributions of transfected cell types were highly dependent on PNP. Cells of the BBB (i.e., endothelial cells, pericytes, and astrocytes) were enriched at 0.2 MPa PNP, while transfection of cells distal to the BBB (i.e., neurons, oligodendrocytes, and microglia) was augmented at 0.4 MPa PNP. PNP-dependent differential gene expression was observed for multiple cell types. Cell stress genes were upregulated proportional to PNP, independent of cell type. Our results underscore how FUS may be tuned to bias transfection toward specific brain cell types in vivo and predict how those cells will respond to transfection.

scholarly journals New Target Genes for the Peroxisome Proliferator-Activated Receptor-γ(PPARγ) Antitumour Activity: Perspectives from the Insulin Receptor

PPAR Research ◽  
2009 ◽  
Vol 2009 ◽  
pp. 1-8 ◽  
Author(s):  
Daniela P. Foti ◽  
Francesco Paonessa ◽  
Eusebio Chiefari ◽  
Antonio Brunetti
Keyword(s):  
Insulin Receptor ◽  
Target Genes ◽  
Tumour Progression ◽  
Antitumour Activity ◽  
Peptide Hormone ◽  
Nuclear Hormone Receptor ◽  
Peroxisome Proliferator ◽  
Preclinical Research ◽  
Peroxisome Proliferator Activated Receptor ◽  
Wide Range

The insulin receptor (IR) plays a crucial role in mediating the metabolic and proliferative functions triggered by the peptide hormone insulin. There is considerable evidence that abnormalities in both IR expression and function may account for malignant transformation and tumour progression in some human neoplasias, including breast cancer. PPARγis a ligand-activated, nuclear hormone receptor implicated in many pleiotropic biological functions related to cell survival and proliferation. In the last decade, PPARγagonists—besides their known action and clinical use as insulin sensitizers—have proved to display a wide range of antineoplastic effects in cells and tissues expressing PPARγ, leading to intensive preclinical research in oncology. PPARγand activators affect tumours by different mechanisms, involving cell proliferation and differentiation, apoptosis, antiinflammatory, and antiangiogenic effects. We recently provided evidence that PPARγand agonists inhibit IR by non canonical, DNA-independent mechanisms affecting IR gene transcription. We conclude that IR may be considered a new PPARγ“target” gene, supporting a potential use of PPARγagonists as antiproliferative agents in selected neoplastic tissues that overexpress the IR.

Molecular markers and antioxidant activity in berry crops: Genetic diversity analysis

2012 ◽  
Vol 92 (6) ◽  
pp. 1121-1133 ◽  
Author(s):  
S. C. Debnath ◽  
Y. L. Siow ◽  
J. Petkau ◽  
D. An ◽  
N. V. Bykova
Keyword(s):  
Genetic Diversity ◽  
Antioxidant Activity ◽  
Molecular Markers ◽  
Molecular Techniques ◽  
Diversity Analysis ◽  
Full Potential ◽  
Genetic Diversity Analysis ◽  
Wide Range ◽  
Berry Crops ◽  
Improvement Programs

Debnath, S. C., Siow, Y. L., Petkau, J., An, D. and Bykova, N. V. 2012. Molecular markers and antioxidant activity in berry crops: Genetic diversity analysis. Can. J. Plant Sci. 92: 1121–1133. An improved understanding of important roles of dietary fruits in maintaining human health has led to a dramatic increase of global berry crop production. Berry fruits contain relatively high levels of vitamin C, cellulose and pectin, and produce anthocyanins, which have important therapeutic values, including antitumor, antiulcer, antioxidant and anti-inflammatory activities. There is a need to develop reliable methods to identify berry germplasm and assess genetic diversity/relatedness for dietary properties in berry genotypes for practical breeding purposes through genotype selection in a breeding program for cultivar development, and proprietary-rights protection. The introduction of molecular biology techniques, such as DNA-based markers, allows direct comparison of different genetic materials independent of environmental influences. Significant progress has been made in diversity analysis of wild cranberry, lowbush blueberry, lingonberry and cloudberry germplasm, and in strawberry and raspberry cultivars and advanced breeding lines developed in Canada. Inter simple sequence repeat (ISSR) markers detected an adequate degree of polymorphism to differentiate among berry genotypes, making this technology valuable for cultivar identification and for the more efficient choice of parents in the current berry improvement programs. Although multiple factors affect antioxidant activity, a wide range of genetic diversity has been reported in wild and cultivated berry crops. Diversity analysis based on molecular markers did not agree with those from antioxidant activity. The paper also discusses the issues that still need to be addressed to utilize the full potential of molecular techniques including expressed sequence tag-polymerase chain reaction (EST-PCR) analysis to develop improved environment-friendly berry cultivars suited to the changing needs of growers and consumers.

Sign in / Sign up

Export Citation Format

Share Document