Inhibition of Murine Cytomegalovirus Infection in Animals by RNase P-Associated External Guide Sequences

Li, Wei; Sheng, Jingxue; Xu, Mengqiong; Vu, Gia-Phong; Zhu, Yan; Sun, Xu; Trang, Phong; Lu, Sangwei; Liu, Fenyong

doi:10.1016/j.omtn.2017.10.007

Cited by 6 publications

(9 citation statements)

References 49 publications

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“…The aforementioned EGS forms were tested in cultured human cells and mice for modulating gene expression and blocking viral infection (Bai et al 2010(Bai et al , 2011Li et al 2017;Deng et al 2019).…”

Section: Human Rnase P and Inactivation Of Gene Expression By Egsmentioning

confidence: 99%

Human RNase P: overview of a ribonuclease of interrelated molecular networks and gene-targeting systems

Jarrous

Liu

2022

RNA

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The seminal discovery of ribonuclease P (RNase P) and its catalytic RNA by Sidney Altman has not only revolutionized our understanding of life, but also opened new fields for scientific exploration and investigation. This review focuses on human RNase P and its use as a gene targeting tool, two topics initiated in Altman’s laboratory. We outline early works on human RNase P as a tRNA processing enzyme and comment on its expanding non-conventional functions in molecular networks of transcription, chromatin remodelling, homology-directed repair and innate immunity. The important implications and insights from these discoveries on the potential use of RNase P as a gene targeting tool are presented. This multifunctionality calls to a modified structure-function partitioning of domains in human RNase P, as well as its relative ribonucleoprotein, RNase MRP. The role of these two catalysts in innate immunity is of particular interest in molecular evolution, as this dynamic molecular network could have originated and evolved from primordial enzymes and sensors of RNA, including predecessors of these two ribonucleoproteins.

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Section: Human Rnase P and Inactivation Of Gene Expression By Egsmentioning

confidence: 99%

Human RNase P: overview of a ribonuclease of interrelated molecular networks and gene-targeting systems

Jarrous

Liu

2022

RNA

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“…In MCMV-infected mice, the EGS variants were more effective in reducing mCSP expression, decreasing viral production, and increasing animal survival, compared with the natural EGS. The results demonstrated that the EGS variant with higher targeting activity in vitro are also more effective in inhibiting MCMV gene expression in mice [49].…”

Section: Egs-rnasementioning

confidence: 94%

“…Li et al explored the antiviral effects of an engineered EGS variant in targeting the shared mRNA sequence which codes for capsid scaffolding proteins (mCSP) and assemblins of murine CMV (MCMV) in the animals [49]. In vitro, the EGS variant was more active in directing RNase P cleavage of the target mRNA than a natural tRNA by 60-fold.…”

Section: Egs-rnasementioning

confidence: 99%

Antiviral Agents as Therapeutic Strategies Against Cytomegalovirus Infections

Chen

Wang

Chen

2019

Viruses

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Cytomegalovirus (CMV) is a threat to human health in the world, particularly for immunologically weak patients. CMV may cause opportunistic infections, congenital infections and central nervous system infections. CMV infections are difficult to treat due to their specific life cycles, mutation, and latency characteristic. Despite recent advances, current drugs used for treating active CMV infections are limited in their efficacy, and the eradication of latent infections is impossible. Current antiviral agents which target the UL54 DNA polymerase are restricted because of nephrotoxicity and viral resistance. CMV also cannot be prevented or eliminated with a vaccine. Fortunately, letermovir which targets the human CMV (HCMV) terminase complex has been recently approved to treat CMV infections in humans. The growing point is developing antiviral agents against both lytically and latently infected cells. The nucleic acid-based therapeutic approaches including the external guide sequences (EGSs)-RNase, the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and transcription activator-like effector nucleases (TALENs) are being explored to remove acute and/or latent CMV infections. HCMV vaccine is being developed for prophylaxis. Additionally, adoptive T cell therapy (ACT) has been experimentally used to combate drug-resistant and recurrent CMV in patients after cell and/or organ transplantation. Developing antiviral agents is promising in this area to obtain fruitful outcomes and to have a great impact on humans for the therapy of CMV infections.

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“…Li and Sheng et al explored the antiviral effects of an EGS variant engineered by in vitro selection procedures using MCMV in an animal model [77]. EGSs were used to target the shared mRNA region of MCMV capsid scaffolding protein (mCSP) and assemblin which is essential for viral progeny production.…”

Section: Egs-rnasementioning

confidence: 99%

“…The results showed that engineered EGS variants with higher targeting activity in vitro are also more effective in inhibiting gene expression in vivo. Furthermore, their findings suggested its possiblility for engineered EGS variants to treat MCMV infections [77].…”

Section: Egs-rnasementioning

confidence: 99%

Potential Therapeutic Approaches Against Brain Diseases Associated with Cytomegalovirus Infections

Wang

Chen

2020

IJMS

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Cytomegalovirus (CMV) is one of the major human health threats worldwide, especially for immunologically comprised patients. CMV may cause opportunistic infections, congenital infections, and brain diseases (e.g., mental retardation and glioblastoma). The etiology of brain diseases associated with human CMV (HCMV) infections is usually complex and it is particularly difficult to treat because HCMV has a life-long infection in its hosts, high mutation rate, and latent infections. Moreover, it is almost impossible to eradicate latent viruses in humans. Although there has been progress in drug discovery recently, current drugs used for treating active CMV infections are still limited in efficacy due to side effects, toxicity, and viral resistance. Fortunately, letermovir which targets the HCMV terminase complex rather than DNA polymerase with fewer adverse reactions has been approved to treat CMV infections in humans. The researchers are focusing on developing approaches against both productive and latent infections of CMV. The gene or RNA targeting approaches including the external guide sequences (EGSs)-RNase, the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and transcription activator-like effector nucleases (TALENs) are being investigated to remove acute and/or latent CMV infections. For the treatment of glioblastoma, vaccine therapy through targeting specific CMV antigens has improved patients’ survival outcomes significantly and immunotherapy has also emerged as an alternative modality. The advanced research for developing anti-CMV agents and approaches is promising to obtain significant outcomes and expecting to have a great impact on the therapy of brain diseases associated with CMV infections.

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Inhibition of Murine Cytomegalovirus Infection in Animals by RNase P-Associated External Guide Sequences

Cited by 6 publications

References 49 publications

Human RNase P: overview of a ribonuclease of interrelated molecular networks and gene-targeting systems

Human RNase P: overview of a ribonuclease of interrelated molecular networks and gene-targeting systems

Antiviral Agents as Therapeutic Strategies Against Cytomegalovirus Infections

Potential Therapeutic Approaches Against Brain Diseases Associated with Cytomegalovirus Infections

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