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

Yb, Deng; Hj, Qin; Yh, Luo; Zr, Liang; Jj, Zou

doi:10.4238/2015.august.21.16

Cited by 9 publications

(5 citation statements)

References 9 publications

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“…Despite an increasing number of successful applications of AST for the treatment of human chronic non-infectious diseases,20, 21, 22, 24, 31, 32, 33, 34, 35, 36, 37 and, more recently, to manage infectious bacteria,37, 38, 39 this methodology was never exploited to control Candida species virulence factors. Moreover, EFG1 has been reported as one of the most relevant virulence determinants involved in C. albicans filamentation and, consequently, in its pathogenicity 6, 10, 11, 12, 13, 14, 15.…”

Section: Resultsmentioning

confidence: 99%

Application of 2′-OMethylRNA′ Antisense Oligomer to Control Candida albicans EFG1 Virulence Determinant

Araújo

Azevedo

Barbosa

et al. 2019

Molecular Therapy - Nucleic Acids

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Antisense oligomers and their analogs have been successfully utilized to silence gene expression for the treatment of many human diseases; however, the control of yeast's virulence determinants has never been exploited before. In this sense, this work is based on the key hypothesis that if a pathogen's genetic sequence is a determinant of virulence, it will be possible to synthesize a nucleic acid mimic based on antisense therapy (AST) that will bind to the mRNA produced, blocking its translation into protein and, consequently, reducing the pathogen virulence phenotype. EFG1 is an important determinant of virulence that is involved in the regulation of the Candida albicans switch from yeast to filamentous form. Thus, our main goal was to design and synthesize an antisense oligonucleotide (ASO) targeting the EFG1 mRNA and to validate its in vitro applicability. The results show that the anti-EFG1 2 0-OMethylRNA (2 0 OMe) oligomer was able to significantly reduce the levels of EFG1 gene expression and of Efg1p protein translation (both approximately 60%), as well as effectively prevent filamentation of C. albicans cells (by 80%). Moreover, it was verified that anti-EFG1 2 0 OMe keeps the efficacy in different simulated human body fluids. Undeniably, this work provides potentially valuable information for future research into the management of Candida infections, regarding the development of a credible and alternative method to control C. albicans infections, based on AST methodology.

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Section: Resultsmentioning

confidence: 99%

Application of 2′-OMethylRNA′ Antisense Oligomer to Control Candida albicans EFG1 Virulence Determinant

Araújo

Azevedo

Barbosa

et al. 2019

Molecular Therapy - Nucleic Acids

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“…Lipid nanoparticles as carriers and adenovirus-mediated RNAi against viral infections have also successfully been applied [ 34 , 35 ]. In vivo studies showed a reduction of hepatitis B virus (HBV) when mice were injected with LNA-modified RNAi therapeutics [ 36 ]. The most prominent use of LNA technology is the clinical candidate miravirsen, where monthly subcutaneously application can downregulate miR-122 and subsequently reduce HCV replication [ 37 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA Regulation of Human Genes Essential for Influenza A (H7N9) Replication

et al. 2016

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Influenza A viruses are important pathogens of humans and animals. While seasonal influenza viruses infect humans every year, occasionally animal-origin viruses emerge to cause pandemics with significantly higher morbidity and mortality rates. In March 2013, the public health authorities of China reported three cases of laboratory confirmed human infection with avian influenza A (H7N9) virus, and subsequently there have been many cases reported across South East Asia and recently in North America. Most patients experience severe respiratory illness, and morbidity with mortality rates near 40%. No vaccine is currently available and the use of antivirals is complicated due the frequent emergence of drug resistant strains. Thus, there is an imminent need to identify new drug targets for therapeutic intervention. In the current study, a high-throughput screening (HTS) assay was performed using microRNA (miRNA) inhibitors to identify new host miRNA targets that reduce influenza H7N9 replication in human respiratory (A549) cells. Validation studies lead to a top hit, hsa-miR-664a-3p, that had potent antiviral effects in reducing H7N9 replication (TCID50 titers) by two logs. In silico pathway analysis revealed that this microRNA targeted the LIF and NEK7 genes with effects on pro-inflammatory factors. In follow up studies using siRNAs, anti-viral properties were shown for LIF. Furthermore, inhibition of hsa-miR-664a-3p also reduced virus replication of pandemic influenza A strains H1N1 and H3N2.

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“…The HBcAg, encoded by the C gene, is found in the core of the nucleocapsid and is a precursor to the secretion of HBeAg [ 39 ]. Deng et al synthesized 3 locked nucleic acids targeted to either the HBV S gene, C gene, or the S/C double gene, encapsulated each in liposomes, and treated HBV transgenic mice [ 40 ]. The results show that all three treatments decreased HBV DNA replication, but the dual-target S/C LNA showed the greatest reduction.…”

Section: Antiviralsmentioning

confidence: 99%

Antisense antimicrobial therapeutics

Sully

Geller

2016

Current Opinion in Microbiology

105

103

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Antisense antimicrobial therapeutics are synthetic oligomers that silence expression of specific genes. This specificity confers an advantage over broad-spectrum antibiotics by avoiding unintended effects on commensal bacteria. The sequence-specificity and short length of antisense antimicrobials also pose little risk to human gene expression. Because antisense antimicrobials are a platform technology, they can be rapidly designed and synthesized to target almost any microbe. This reduces drug discovery time, and provides flexibility and a rational approach to drug development. Recent work has shown that antisense technology has the potential to address the antibiotic-resistance crisis, since resistance mechanisms for standard antibiotics apparently have no effect on antisense antimicrobials. Here, we describe current reports of antisense antimicrobials targeted against viruses, parasites, and bacteria.

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

Cited by 9 publications

References 9 publications

Application of 2′-OMethylRNA′ Antisense Oligomer to Control Candida albicans EFG1 Virulence Determinant

Application of 2′-OMethylRNA′ Antisense Oligomer to Control Candida albicans EFG1 Virulence Determinant

MicroRNA Regulation of Human Genes Essential for Influenza A (H7N9) Replication

Antisense antimicrobial therapeutics

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