scholarly journals Small Drugs, Huge Impact: The Extraordinary Impact of Antisense Oligonucleotides in Research and Drug Development

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 536
Author(s):  
Anais M. Quemener ◽  
Maria Laura Centomo ◽  
Scott L. Sax ◽  
Riccardo Panella

Antisense oligonucleotides (ASOs) are an increasingly represented class of drugs. These small sequences of nucleotides are designed to precisely target other oligonucleotides, usually RNA species, and are modified to protect them from degradation by nucleases. Their specificity is due to their sequence, so it is possible to target any RNA sequence that is already known. These molecules are very versatile and adaptable given that their sequence and chemistry can be custom manufactured. Based on the chemistry being used, their activity may significantly change and their effects on cell function and phenotypes can differ dramatically. While some will cause the target RNA to decay, others will only bind to the target and act as a steric blocker. Their incredible versatility is the key to manipulating several aspects of nucleic acid function as well as their process, and alter the transcriptome profile of a specific cell type or tissue. For example, they can be used to modify splicing or mask specific sites on a target. The entire design rather than just the sequence is essential to ensuring the specificity of the ASO to its target. Thus, it is vitally important to ensure that the complete process of drug design and testing is taken into account. ASOs’ adaptability is a considerable advantage, and over the past decades has allowed multiple new drugs to be approved. This, in turn, has had a significant and positive impact on patient lives. Given current challenges presented by the COVID-19 pandemic, it is necessary to find new therapeutic strategies that would complement the vaccination efforts being used across the globe. ASOs may be a very powerful tool that can be used to target the virus RNA and provide a therapeutic paradigm. The proof of the efficacy of ASOs as an anti-viral agent is long-standing, yet no molecule currently has FDA approval. The emergence and widespread use of RNA vaccines during this health crisis might provide an ideal opportunity to develop the first anti-viral ASOs on the market. In this review, we describe the story of ASOs, the different characteristics of their chemistry, and how their characteristics translate into research and as a clinical tool.

2016 ◽  
Vol 04 (01) ◽  
pp. 1640001 ◽  
Author(s):  
Ying Wan ◽  
Xing Li ◽  
Shenqi Wang

Biohybrid materials play an important role in tissue engineering, artificial organs and regenerative medicine due to their regulation of cell function through specific cell–matrix interactions involving integrins, mostly those of fibroblasts and myofibroblasts, and ligands on the matrix surface, which have become current research focus. In this paper, recent progress of biohybrid materials, mainly including main types of biohybrid materials, rapid prototype (RP) technique for construction of 3D biohybrid materials, was reviewed in detail; moreover, their applications in tissue engineering, artificial organs and regenerative medicine were also reviewed in detail. At last, we address the challenges biohybrid materials may face.


2020 ◽  
Vol 10 (3) ◽  
pp. 5392-5399

Plants with medicinal properties possess beneficial influences on health and disease. Different plant parts and extracts carry valuable active ingredients with pharmacological properties that lead to developing new drugs. Terminalia bellirica is among those plants that have been formulated as pharmaceutical products. This is attributed to its biologically active phenolics and tannins exhibiting analgesic, anti-hypertensive, anti-microbial, anti-diabetic, anti-oxidant, as well as, other pharmacological properties. Beetroot has been shown to be rich in nitrates with a positive impact on the cardiovascular system. Beetroot contains a number of useful ingredients as the free-radical scavenger ascorbic acid, the anti-inflammatory flavonoids and the anti-oxidant carotenoids. Moreover, beetroot is rich in the natural colorant betalains that are further classified into betacyanins and betaxanthins. Betanin, is one of the major constituents of beetroots that have been postulated to possess significant beneficial therapeutic effects in a number of conditions and diseases. However, several studies have demonstrated the relatively poor bioavailability of betanin upon oral administration. In the current review we aim to highlight some of the latest researches dealing with the therapeutic properties of betanin in different disease conditions, the possible mechanistic pathways beyond such beneficial effects and plausible strategies capable of enhancing its stability and bioavailability.


2021 ◽  
Vol 7 (1) ◽  
pp. 36
Author(s):  
Soedarsono Soedarsono

Tuberculosis (TB) still becomes a public health crisis. Drug-resistant TB (DR-TB) becomes a concern as the increasing DR-TB cases in countries with high TB burden. The 2017 World Health Organization (WHO) guideline recommended a combination of TB treatment consisting of 2 months of intensive phase with isoniazid (H), rifampisin (R), pyrazinamid (Z), and ethambutol (E), followed by 4 months of continuation phase with HR daily. WHO has updated DR-TB treatment guidelines several times. In 2016, WHO recommended shorter regimen and individual regimen based on certain conditions. The most updated 2020 WHO guideline recommended the short regimen consisting of all oral drugs as well as changes in the grouping of medicines used in DR-TB regimens in longer/individual regimens. Bedaquiline, delamanid, pretomanid, and sutezolid are new drugs which have been studied for their uses as anti-TB drugs (ATD). Bedaquilin and delamanid, which have passed phase 3 trials, have been approved and recommended by WHO for DR-TB treatment. Repurposed drugs have been used for DR-TB treatment during the time of evaluation of drugs list and regimens for DR-TB treatment. Fluoroquinolones, clofazimine, linezolid, carbapenem, amoxicillin/clavulanic acid are repurposed drugs. TB and DR-TB management will be updated at any time, based on the latest findings in studies, to evaluate and improve the effectiveness of current treatments. Prevention of active TB disease by the treatment of latent TB infection (LTBI) is also a critical component of the end TB strategy by WHO. Therefore, the development of new drugs for the LTBI treatment is also needed.


Lupus ◽  
2020 ◽  
Vol 29 (13) ◽  
pp. 1661-1672
Author(s):  
Alice Mason ◽  
Emily Rose ◽  
Christopher J Edwards

Severe acute respiratory syndrome coronavirus (SARS-CoV-2), the virus causing Coronavirus disease 2019 (COVID-19), has had a huge impact on health services with a high mortality associated with complications including pneumonia and acute respiratory distress syndrome. Historical evidence suggests that Lupus patients have a higher incidence of several viral infections. This is likely due to a combination of immune dysfunction, immunosuppressive therapy and excess co-morbidities. In this context there has been concern that Lupus patients may be at a higher risk of developing COVID-19 and suffering a severe disease course. As a result, many Lupus patients have been advised to ‘shield’ by isolating from social contact in the hope that this will reduce the likelihood of infection. Early clinical data does not appear to show that the incidence of COVID-19 is higher in Lupus patients. Reassuringly, the clinical course of COVID-19 in Lupus does not generally seem to be more severe than in the general population. There has been huge interest in repurposing existing drugs as potential treatments, including several used to treat Lupus. Of these, corticosteroids and hydroxychloroquine are the most well researched so far. The current evidence suggests that the corticosteroid dexamethasone improves outcome for the sickest COVID-19 patients requiring respiratory support. Initial reports suggested that hydroxychloroquine could have a positive impact on the course of COVID-19, however larger prospective studies have not supported this. Janus kinase inhibitors, currently being investigated for efficacy in lupus, have been shown to have anti-viral effects in vitro and inhibiting the JAK-STAT pathway may dampen down the host hyper-inflammatory response. Several trials are ongoing to assess the outcome of the use of JAK inhibitors in COVID-19 positive patients. For most patients continuing with their existing therapies to prevent a lupus flare or adverse events associated with sudden corticosteroid withdrawal is important whilst an Individualised risk assessment remains vital.


2020 ◽  
Vol 22 (2) ◽  
pp. 192-196 ◽  
Author(s):  
Anant Kumar

The COVID-19 pandemic and subsequent lockdown to mitigate the spread of the pandemic has led to social isolation, reduced social support system and increased cases of domestic violence against women. The United Nations and other international and national agencies speculate further increase in it and have suggested governments to take appropriate action to safeguard the health and human rights of women. Many governments have also taken steps and working towards it by starting helpline and counselling services. This article reviews the concerns raised by these agencies, interventions introduced and its future implications. It also argues that apart from reported cases of domestic violence and its negative consequences on individuals and families, it would be interesting to study the positive impact of living together as this pandemic is different from other emergencies. The sociologist Marianne Hester argued that ‘domestic violence goes up whenever families spend more time together’. It would be interesting to study and examine it in the context of COVID-19 pandemic. This article also suggests the need for further research to understand the reason and dynamics of such violence considering men and women both are engaged in such violence against each other and bear its consequences together.


2021 ◽  
Author(s):  
Shihao Ding ◽  
Bingting Yu ◽  
Anneke van Vuuren

Abstract Despite the huge impact of rotavirus infection on global public health, there is no normally available drug against the virus worldwide. We have revealed the interaction of cholesterol metabolism and rotavirus replication, as well as identified statin as a promising drug to repress rotavirus infection, but the medical resources are greatly different across countries, so more drugs are needed for anti-rotavirus treatment in clinical activity. Two cell lines and a human small intestinal organoids were used as the models, which were infected by rotavirus SA11 strain. A clinically derived rotavirus virion, 026K strain, was measured intracellular virus RNA copies in Caco2 cells. We investigated the effects of different cholesterol-lowering drugs, including bisphosphonates (zoledronic acid, ZA), fibrate class (fenofibric acid, FA), vitamin B3 (nicotinic acid, NA), and ezetimibe on rotavirus replication in the pre-clinical models. All these cholesterol-lowering drugs resulted in significant decreases of rotavirus replication. The combinations of FA / ezetimibe with the statins had not the obvious synergies in the inhibition of rotavirus replication than any of them alone. Compared to the other drugs, ezetimibe showed the additional preventive and interference effects towards rotavirus infection. We describe an emerging application of clinical cholesterol-lowering therapy for anti-rotavirus treatment. These results could be directly considered when physicians treat with rotavirus-caused diseases worldwide.


Author(s):  
F. S. Fay ◽  
Kevin Fogarty ◽  
Richard Tuft ◽  
Walter Carrington

Many current questions in cell biology revolve around questions regarding how changes in cell function are caused by changes in their molecular composition. Given that cells are highly organized structures often carrying out diverse functions in different compartments, it follows that changes in specific cell functions must involve highly localized changes in molecular composition.We have been involved in the development of the digital imaging microscope as a tool to investigate the distribution of molecules inside single living cells. The system measures fluorescence of probes that are highly fluorescent and specific for a molecule or ion of interest and utilizes a wide-field rather than a confocal microscope to produce an image of fluorescence in a single cell. The image is captured by a high quantum efficiency, low noise cooled CCD, thereby providing ultrahigh efficiency in the acquisition of fluorescent images. By utilizing very powerful light sources, the system is capable of generating an image with good signal-to-noise ratio in a millisecond or less, thereby allowing one to follow extremely rapid changes in molecular or ion distribution in single cells.


2018 ◽  
Author(s):  
Yu.A. Bykovskii ◽  
A  Yanchenko ◽  
M  Azopkov ◽  
V  Golubovich ◽  
S  Fefelova ◽  
...  

Цель исследований: оценка эффективности инкрустирования семян столовых корнеплодов рядом новых препаратов, его влияния на посевные качества: энергию прорастания, лабораторную всхожесть, полевую всхожесть. Опыты проводили лабораторных и полевых условиях в Быковском расширении Москворецкой поймы (Раменский район Московской области) по стандартным методикам: ГОСТ 120036–85 «Семена сельскохозяйственных культур. Правила приемки и методы отбора проб», ГОСТ 12038–84 «Семена сельскохозяйственных культур. Методы определения всхожести». Посевные качества оценивали по ГОСТ 32917–2014 «Семена овощных культур и кормовой свеклы дражированные. Посевные качества. Общие технические условия». Лабораторно-полевые опыты проводили по методикам, изложенным в книге «Методика опытного дела в овощеводстве и бахчеводстве» под редакцией С.С. Литвинова. В качестве кремнеауксиновых регуляторов роста использованы препараты Энергия-М (в качестве стандарта), Энербат, Силабат, ОКМ (органический комплекс меди), Крезабат. В результате исследований были получены экспериментальные данные о том, что включение новых кремнеауксиновых регуляторов роста в оболочку дражированных семян моркови столовой неодинаково влияет на их всхожесть и густоту стояния растений. Использование препарата Крезабат отрицательно сказалось на урожайности столовой моркови и ее сохраняемости. Включение в состав оболочки дражированных семян столовой моркови кремнеауксиновых препаратов незадолго до посева не снижает посевных качеств семян: энергии прорастания и лабораторной всхожести, но увеличивает полевую всхожесть. Применение препаратов Энербат и ОКМ (органический комплекс меди) положительно сказалось на сохраняемости посевов столовой моркови. Наибольшая прибавка стандартных корнеплодов была получена в варианте с применением препарата Энербат. Однако существенную прибавку по отношению к контролю дали также варианты Силабат и ОКМ.The purpose of the research: to evaluate the effectiveness of seed root crops encrusting with a number of new drugs, its impact on the sowing qualities: germination energy, laboratory germination, field germination. Experiments were carried out under laboratory and field conditions in the Bykovo expansion of Moscow river floodplain (Ramensky district, Moscow region) according to standard methods: GOST 120036–85: Seeds of agricultural crops. Acceptance rules and sampling methods, GOST 12038–84: Seeds of agricultural crops. Methods for determination of germination. Sowing qualities were assessed according to GOST 32917–2014: Vegetable seeds and fodder beet pelleted seeds. Sowing qualities. General specifications. Laboratory field experiments were carried out according to the methods described in the «Methods of experimental work in vegetable and melon production» edited by S. Litvinov. As growth regulators preparations Energia-M (as standard), Enerbat, Silabat, OKM (organic complex of copper), Crezabat were used. As a result of the research was experimental evidence that the inclusion of new growth regulators in the shell pelleted seeds carrot unequally affects germination and plant density. The use of the Krezabat preparation had a negative impact on the yield of carrot and its persistence. The inclusion in the composition of the shell pelleted seeds of carrot silicon auxin preparations shortly before seeding did not reduce sowing qualities of seeds: germination energy and laboratory germination, but increases germination. The use of Enerbat and OKM (organic complex of copper) preparations had a positive impact on the persistence of the crops of carrot. The greatest rise in standard of roots was obtained in the variant with use of the Enerbat preparations. However, a significant increase relative to the control were also options Silabat and OKM.


2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Kashef A. Majid ◽  
David W. Kolar ◽  
Michel Laroche

Purpose Crises threaten the operations of small businesses and endanger their survival; however, when the crisis is not attributable to the firm, consumers may rally around the business. This study aims to examine how attitudes toward helping others can create support for small businesses, which in turn can direct consumers to help businesses with increased financial support. It is hoped that this paper will inform how consumers will help firms pivot during crises. Design/methodology/approach A conceptual model was proposed which linked support for helping others to increased willingness to tip/amount tipped. The model was tested using structural equation modeling from two surveys given to customers of two small businesses, a coffee shop and an independent movie theater, respectively. Findings During a crisis, support for helping others has a positive impact on feelings of support for small businesses. Consumers direct their support to small businesses that they are interested in seeing survive and continue operations. They either tip more or tip when they otherwise would not have tipped. Practical implications Firms that pivot their operations because of a crisis imposed on them can still generate revenues. Consumers who have a self-interest in the continuing operations of the firm want to support it, and by pivoting their business model, the firm gives consumers the opportunity to give the firm and its employees more than they would have in the form of tips. Originality/value Prior work in crisis management has focused primarily on how firms recover and respond to a crisis of their doing. Overwhelmingly, consumers have been shown to punish firms during times of crisis. However, for a crisis that is imposed on the firm, consumers may rally behind the firm and respond by supporting it more than they are required to.


2007 ◽  
Vol 342-343 ◽  
pp. 197-200 ◽  
Author(s):  
Chang Hyun Ahn ◽  
Young Jin Kim ◽  
Inn Kyu Kang ◽  
Ga Young Jun ◽  
Young Gwang Ko ◽  
...  

In this study, we prepared polystyrene (PS) nanofibers as hepatocytes culture substrates by electrospinning method and subsequently coated with specific ligand (poly(N--vinylbenzyl-- β-D-galactopyranosyl-(14)-D-gluconamide)(PVLA) for hepatocytes attachment. Rat hepatocytes’ behavior on the PVLA-coated and non-coated PS nanofibrous matrices have been investigated. Electrospun PS fiber structures revealed randomly aligned fibers with average diameter of 500 nm. Fabricated PS nanofibers had no bonding points like cotton fibers. Analyses by ATR/FTIR and ESCA revealed that PVLA was successfully coated to the surfaces of PS nanofibers. More hepatocytes were attached on the surface of PS nanofibers coated with PVLA than that on noncoated PS nanofibers. PS nanofibrous matrix could incorporate many cells into the interior of the matrix probably due to the suitable pore size. Cell viabilities cultured on PVLA-coated PS nanofibrous mats were maintained for 2 weeks, while it was decreased rapidly on PVLA-coated PS dishes. High hepatic function especially albumin secretion was maintained for 2 weeks on nanofibrous mats but rapidly decreased on flat PS dishes. These results indicate that nanofibrous structure enabled spheroid-like culture results in providing cell-cell communication and subsequent long-term maintenance of specific cell function.


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