Deliver the promise: RNAs as a new class of molecular entities for therapy and vaccination

Yu, Ai Ming; Tu, Mei Juan

doi:10.1016/j.pharmthera.2021.107967

Cited by 52 publications

(54 citation statements)

References 327 publications

(440 reference statements)

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“…In this context, the RNA polymerase inhibitor remdesivir and antibody preparations have been approved for the treatment of COVID-19 patients, but their efficacy appears to be limited [ 28 ]. Moreover, other direct antiviral approaches such as antisense strategies are under development for respiratory viruses such as SARS-CoV-2 [ 38 , 39 , 40 ] but are not yet clinically available as treatment options for COVID-19. Hence, effective additional antiviral treatment options are needed, and combinations of metabolic drugs such as 2DG and BOT may play a role in COVID-19 therapies in the future.…”

Section: Discussionmentioning

confidence: 99%

“…Notably, a metabolic shift towards glycolysis and PPP may also be involved in the inflammatory processes that are associated with COVID-19 progression to severe, life-threatening disease stages [ 9 , 43 , 44 , 45 ]. Moreover, reports show that a number of COVID-19 survivors suffer from metabolic disorders including abnormal glucose metabolism resulting in the metabolic derailment of immune cells [ 40 ]. Therefore, targeting the host cell metabolism by drug combinations such as BOT and 2DG may not only inhibit SARS-CoV-2 replication but also alleviate COVID-19 severity by immunomodulatory activity.…”

Section: Discussionmentioning

confidence: 99%

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Targeting the Pentose Phosphate Pathway for SARS-CoV-2 Therapy

et al. 2021

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SARS-CoV-2 is causing the coronavirus disease 2019 (COVID-19) pandemic, for which effective pharmacological therapies are needed. SARS-CoV-2 induces a shift of the host cell metabolism towards glycolysis, and the glycolysis inhibitor 2-deoxy-d-glucose (2DG), which interferes with SARS-CoV-2 infection, is under development for the treatment of COVID-19 patients. The glycolytic pathway generates intermediates that supply the non-oxidative branch of the pentose phosphate pathway (PPP). In this study, the analysis of proteomics data indicated increased transketolase (TKT) levels in SARS-CoV-2-infected cells, suggesting that a role is played by the non-oxidative PPP. In agreement, the TKT inhibitor benfooxythiamine (BOT) inhibited SARS-CoV-2 replication and increased the anti-SARS-CoV-2 activity of 2DG. In conclusion, SARS-CoV-2 infection is associated with changes in the regulation of the PPP. The TKT inhibitor BOT inhibited SARS-CoV-2 replication and increased the activity of the glycolysis inhibitor 2DG. Notably, metabolic drugs like BOT and 2DG may also interfere with COVID-19-associated immunopathology by modifying the metabolism of immune cells in addition to inhibiting SARS-CoV-2 replication. Hence, they may improve COVID-19 therapy outcomes by exerting antiviral and immunomodulatory effects.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Targeting the Pentose Phosphate Pathway for SARS-CoV-2 Therapy

et al. 2021

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“…Likewise, inotersen was developed to reduce hepatic TTR protein synthesis and serum TTR levels through RNAse H-mediated degradation of mutant and wild-type TTR mRNAs following complementary base pairing [ 43 ]. Inotersen is a 2′-MOE-modified antisense oligonucleotide (ASO) that uses short synthetic single-stranded DNA molecules to alter the splicing process.…”

Section: Novel Treatments For Attr Amyloidosismentioning

confidence: 99%

A Brief Journey through Protein Misfolding in Transthyretin Amyloidosis (ATTR Amyloidosis)

González‐Duarte

Ulloa‐Aguirre

2021

IJMS

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Transthyretin (TTR) amyloidogenesis involves the formation, aggregation, and deposition of amyloid fibrils from tetrameric TTR in different organs and tissues. While the result of amyloidoses is the accumulation of amyloid fibrils resulting in end-organ damage, the nature, and sequence of the molecular causes leading to amyloidosis may differ between the different variants. In addition, fibril accumulation and toxicity vary between different mutations. Structural changes in amyloidogenic TTR have been difficult to identify through X-ray crystallography; but nuclear magnetic resonance spectroscopy has revealed different chemical shifts in the backbone structure of mutated and wild-type TTR, resulting in diverse responses to the cellular conditions or proteolytic stress. Toxic mechanisms of TTR amyloidosis have different effects on different tissues. Therapeutic approaches have evolved from orthotopic liver transplants to novel disease-modifying therapies that stabilize TTR tetramers and gene-silencing agents like small interfering RNA and antisense oligonucleotide therapies. The underlying molecular mechanisms of the different TTR variants could be responsible for the tropisms to specific organs, the age at onset, treatment responses, or disparities in the prognosis.

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“…It remains to be explored whether circPVT1 binds to which miRNA plays the most important role. Thirdly, many studies have reported that ncRNAs have the potential to be developed as reagents for clinical treatment [ 75 , 76 ],whether circPVT1 can be used as a therapeutic target for corresponding research and development still needs a lot of experimental proof. Moreover, we also need to collect more clinical specimens to explore the clinical application potential of circPVT1 .…”

Section: Discussionmentioning

confidence: 99%

Circular RNA Pvt1 oncogene (CircPVT1) promotes the progression of papillary thyroid carcinoma by activating the Wnt/β-catenin signaling pathway and modulating the ratio of microRNA-195 (miR-195) to vascular endothelial growth factor A (VEGFA) expression

Zeng¹,

Yuan²,

Zhou³

et al. 2021

Bioengineered

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Circular RNAs (circRNAs) have been reported to be involved in the progression of papillary thyroid carcinoma (PTC). However, the role of circular RNA Pvt1 oncogene ( circPVT1) in PTC has rarely been reported. In this study, we aimed to investigate the function and mechanism of circPVT1 in PTC. The expression level of circPVT1, miR-195 and VEGFA were determined by reverse transcription‑quantitative PCR (RT‑qPCR). Fisher’s exact test was used to analyze the correlation between circPVT1 expression and PTC clinical features. Cell Counting Kit-8 (CCK-8) and 5-Ethynyl-2ʹ-deoxyuridine (EdU) staining assay and transwell assay were conducted to evaluate the cell proliferation, migration and invasion ability. Dual-luciferase reporter and Western blot assay were conducted for evaluating the correlation between miR-195 and circPVT1 or VEGFA . The results of RT-PCR showed that the expression level of circPVT1 was significantly upregulated in PTC tissues and cell lines. After downregulating circPVT1 expression in PTC cells, the abilities of cell proliferation, migration, and invasion were obviously suppressed, and the Wnt/β-catenin signaling pathway was also repressed. Besides, miR-195 could both bind to PVT1 and VEGFA , while PVT1 could promote the expression of VEGFA by binding to miR-195 . Downregulation of VEGFA expression in PTC cells revealed weakened cell proliferation, migration, and invasion capacities, and restrained Wnt/β-catenin signaling pathway. Therefore, we demonstrated that circPVT1 could promote VEGFA expression by sponging miR-195. CircPVT1 could serve as a molecule sponge for miR-195 and mediate the ceRNA network to promote the expression of VEGFA , thus contributed to the malignant progression of PTC.

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Deliver the promise: RNAs as a new class of molecular entities for therapy and vaccination

Cited by 52 publications

References 327 publications

Targeting the Pentose Phosphate Pathway for SARS-CoV-2 Therapy

Targeting the Pentose Phosphate Pathway for SARS-CoV-2 Therapy

A Brief Journey through Protein Misfolding in Transthyretin Amyloidosis (ATTR Amyloidosis)

Circular RNA Pvt1 oncogene (CircPVT1) promotes the progression of papillary thyroid carcinoma by activating the Wnt/β-catenin signaling pathway and modulating the ratio of microRNA-195 (miR-195) to vascular endothelial growth factor A (VEGFA) expression

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