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Fulltext Oligonucleotide therapy: An emerging focus area for drug delivery in chronic inflammatory respiratory diseases

Mehta M, Deeksha, Tewari D, Gupta G, Awasthi R, Singh H, et al.

Chem Biol Interact, 2019 Aug 01;308:206-215.
PMID: 31136735 DOI: 10.1016/j.cbi.2019.05.028

Oligonucleotide-based therapies are advanced novel interventions used in the management of various respiratory diseases such as asthma and Chronic Obstructive Pulmonary Disease (COPD). These agents primarily act by gene silencing or RNA interference. Better methodologies and techniques are the need of the hour that can deliver these agents to tissues and cells in a target specific manner by which their maximum potential can be reached in the management of chronic inflammatory diseases. Nanoparticles play an important role in the target-specific delivery of drugs. In addition, oligonucleotides also are extensively used for gene transfer in the form of polymeric, liposomal and inorganic carrier materials. Therefore, the current review focuses on various novel dosage forms like nanoparticles, liposomes that can be used efficiently for the delivery of various oligonucleotides such as siRNA and miRNA. We also discuss the future perspectives and targets for oligonucleotides in the management of respiratory diseases.

Matched MeSH terms: Oligonucleotides, Antisense/therapeutic use*; Oligonucleotides, Antisense/chemistry
Resolution of coronavirus disease 2019 (COVID-19)

Habas K, Nganwuchu C, Shahzad F, Gopalan R, Haque M, Rahman S, et al.

Expert Rev Anti Infect Ther, 2020 12;18(12):1201-1211.
PMID: 32749914 DOI: 10.1080/14787210.2020.1797487

INTRODUCTION: Coronavirus disease 2019 (COVID-19) was first detected in China in December, 2019, and declared as a pandemic by the World Health Organization (WHO) on March 11, 2020. The current management of COVID-19 is based generally on supportive therapy and treatment to prevent respiratory failure. The effective option of antiviral therapy and vaccination are currently under evaluation and development.
AREAS COVERED: A literature search was performed using PubMed between December 1, 2019-June 23, 2020. This review highlights the current state of knowledge on the viral replication and pathogenicity, diagnostic and therapeutic strategies, and management of COVID-19. This review will be of interest to scientists and clinicians and make a significant contribution toward development of vaccines and targeted therapies to contain the pandemic.
EXPERT OPINION: The exit strategy for a path back to normal life is required, which should involve a multi-prong effort toward development of new treatment and a successful vaccine to protect public health worldwide and prevent future COVID-19 outbreaks. Therefore, the bench to bedside translational research as well as reverse translational works focusing bedside to bench is very important and would provide the foundation for the development of targeted drugs and vaccines for COVID-19 infections.

Matched MeSH terms: Oligonucleotides, Antisense/therapeutic use
Fulltext Pbx1 is essential for growth of zebrafish swim bladder

Teoh PH, Shu-Chien AC, Chan WK

Dev. Dyn., 2010 Mar;239(3):865-74.
PMID: 20108353 DOI: 10.1002/dvdy.22221

pbx1, a TALE (three-amino acid loop extension) homeodomain transcription factor, is involved in a diverse range of developmental processes. We examined the expression of pbx1 during zebrafish development by in situ hybridization. pbx1 transcripts could be detected in the central nervous system and pharyngeal arches from 24 hpf onwards. In the swim bladder anlage, pbx1 was detected as early as 28 hpf, making it the earliest known marker for this organ. Morpholino-mediated gene knockdown of pbx1 revealed that the swim bladder failed to inflate, with eventual lethality occurring by 8 dpf. The knockdown of pbx1 did not perturb the expression of prdc and foxA3, with both early swim bladder markers appearing normally at 36 and 48 hpf, respectively. However, the expression of anxa5 was completely abolished by pbx1 knockdown at 60 hpf suggesting that pbx1 may be required during the late stage of swim bladder development.

Matched MeSH terms: Oligonucleotides, Antisense/metabolism
Effect of antisense oligodeoxynucleotides for ICAM-1 on renal ischaemia-reperfusion injury in the anaesthetised rat

Kiew LV, Munavvar AS, Law CH, Azizan AN, Nazarina AR, Sidik K, et al.

J Physiol, 2004 Jun 15;557(Pt 3):981-9.
PMID: 15047774

An antisense oligodeoxynucleotide (As-ODN) to the 3' untranslated region of the mRNA sequence expressing the intracellular adhesion molecule-1 (ICAM-1) was employed to determine ICAM-1's role in renal ischaemia-reperfusion injury in the rat. Wistar-Kyoto rats receiving i.v. either lipofectin-As-ODN (As-ODN group), lipofectin-reverse ODN (Rv-ODN group) or lipofectin (ischaemia control group) 8 h prior to study were anaesthetized and subjected to 30 min of renal artery occlusion. Renal haemodynamic and excretory parameters were monitored before and after renal ischaemia. On termination of the study renal tissue was subjected to histological and Western blot analysis. Renal blood flow decreased in the 3 h post-ischaemia period in the ischaemia control and Rv-ODN groups, but was maintained in the As-ODN group. Glomerular filtration rate was depressed initially but gradually increased to 10% above basal levels in the ischaemia control and Rv-ODN groups, but was below basal levels (20%) in the As-ODN group. There was a three- to fourfold increase in sodium and water excretion following ischaemia in the ischaemia control and reverse-ODN groups but not in the As-ODN treated group. The As-ODN ameliorated the histological evidence of ischaemic damage and reduced ICAM-1 protein levels to a greater extent in the medulla than cortex. These observations suggested that in the post-ischaemic period afferent and efferent arteriolar tone was increased with a loss of reabsorptive capacity which was in part due to ICAM-1. The possibility arises that the action of ICAM-1 at vascular and tubular sites in the deeper regions of the kidney contributes to the ischaemia-reperfusion injury.

Matched MeSH terms: Oligonucleotides, Antisense/therapeutic use*
Fulltext Effect of TGF-beta1 antisense oligodeoxynucleotide on renal function in chronic renal failure rats

Hiong LC, Voon KL, Abdullah NA, Sattar MA, Rahman NA, Khan AH, et al.

Acta Pharmacol Sin, 2008 Apr;29(4):451-7.
PMID: 18358091 DOI: 10.1111/j.1745-7254.2008.00772.x

The aim of the present study was to investigate the effectiveness of transforming growth factor (TGF)-beta1 antisense oligodeoxynucleotides (ODN) in ameliorating deteriorated kidney function in rats with puromycin-induced chronic renal failure (CRF).

Matched MeSH terms: Oligonucleotides, Antisense/pharmacology*