Disrupting autorepression circuitry generates “open-loop lethality” to yield escape-resistant antiviral agents

Chaturvedi, Sonali; Pablo, Michael; Wolf, Marie; Rosas-Rivera, Daniel; Calia, Giuliana; Kumar, Arjun J; Vardi, Noam; Du, Kelvin; Glazier, Joshua; Ke, Ruian; Chan, Matilda F.; Perelson, Alan S.; Weinberger, Leor S.

doi:10.1016/j.cell.2022.04.022

Cited by 7 publications

(2 citation statements)

References 123 publications

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“…Relying on the DNA-PK activation-dependent intrinsic immune response to IFN regulatory factor 3 (IRF-3) [ 94 , 95 ], the combined DNA-PK inhibitors blocked DNA-PK pathway and decreased IRF-3 to promote the proliferation and expansion of OV M1 in tumor cells. In a recent study, the Weinberger group [ 96 ] proposed a strategy to disrupt the feedback loop of herpesviruses using an engineered DNA duplex, causing the host cell to “overload” and die and also dismantling the barrier to drug resistance.…”

Section: Ov-activated Immune Responses For Realizing Immunotherapymentioning

confidence: 99%

Emerging Nano-/Biotechnology Drives Oncolytic Virus-Activated and Combined Cancer Immunotherapy

et al. 2023

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Oncolytic viruses (OVs) as one promising antitumor methods have made important contributions to tumor immunotherapy, which arouse increasing attention. They provide the dual mechanisms including direct killing effect toward tumor cells and immune activation for elevating antitumor responses, which have been proved in many preclinical studies. Especially, natural or genetically modified viruses as clinical immune preparations have emerged as a new promising approach objective to oncology treatment. The approval of talimogene laherparepvec (T-VEC) by the U.S. Food and Drug Administration (FDA) for the therapy of advanced melanoma could be considered as a milestone achievement in the clinical translation of OV. In this review, we first discussed the antitumor mechanisms of OVs with an emphasis on targeting, replication, and propagation. We further outlined the state of the art of current OVs in tumor and underlined the activated biological effects especially including immunity. More significantly, the enhanced immune responses based on OVs were systematically discussed from different perspectives such as combination with immunotherapy, genetic engineering of OVs, integration with nanobiotechnology or nanoparticles, and antiviral response counteraction, where their principles were shed light on. The development of OVs in the clinics was also highlighted to analyze the actuality and concerns of different OV applications in clinical trials. At last, the future perspectives and challenges of OVs as an already widely accepted treatment means were discussed. This review will provide a systematic review and deep insight into OV development and also offer new opportunities and guidance pathways to drive the further clinical translation.

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Section: Ov-activated Immune Responses For Realizing Immunotherapymentioning

confidence: 99%

Emerging Nano-/Biotechnology Drives Oncolytic Virus-Activated and Combined Cancer Immunotherapy

et al. 2023

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“…In a recent paper, Chaturvedi et al published a study in Cell reporting that the artificially synthesized nucleic acid decoys would disrupt the autorepression, which can generate antiviral agents with a high barrier to the evolution of resistance 1 (Fig. 1 ).…”

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confidence: 99%

Cis-regulatory decoy disrupts autorepression: a potential escape-resistant anti-viral therapy

Hu¹,

Min

Sun

2022

Sig Transduct Target Ther

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New antivirals exploit viral feedback tricks for a cure without resistance

Balázsi¹

2022

Cell

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Disrupting autorepression circuitry generates “open-loop lethality” to yield escape-resistant antiviral agents

Cited by 7 publications

References 123 publications

Emerging Nano-/Biotechnology Drives Oncolytic Virus-Activated and Combined Cancer Immunotherapy

Emerging Nano-/Biotechnology Drives Oncolytic Virus-Activated and Combined Cancer Immunotherapy

Cis-regulatory decoy disrupts autorepression: a potential escape-resistant anti-viral therapy

New antivirals exploit viral feedback tricks for a cure without resistance

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