Targeted Nanoparticle Delivery of Bifunctional RIG-I Agonists to Pancreatic Cancer

Zillinger, Thomas; Hartmann, Gunther

doi:10.1016/j.ymthe.2019.02.005

Cited by 6 publications

(4 citation statements)

References 13 publications

(15 reference statements)

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“…We suggest that intravenous 3pRNA results in ISG induction in PBMCs, which could promote recruitment of activated leukocytes to the lung. Moreover, given that intravenous 3pRNA primarily localizes to the liver, spleen and lung [ 40 ], direct delivery to parenchymal cells in the lung might also induce ISGs and therefore protection against RSV.…”

Section: Discussionmentioning

confidence: 99%

Retinoic Acid–Inducible Gene I Activation Inhibits Human Respiratory Syncytial Virus Replication in Mammalian Cells and in Mouse and Ferret Models of Infection

Schwab

Farrukee

Eléouët

et al. 2022

The Journal of Infectious Diseases

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Infections caused by human respiratory syncytial virus (RSV) are associated with substantial morbidity and mortality. Treatment options are limited and there is urgent need for the development of efficient antivirals. Pattern recognition receptors such as the cytoplasmic helicase retinoic-acid-inducible gene (RIG)-I can be activated by viral nucleic acids, leading to activation of interferon-stimulated genes and generation of an ‘antiviral state’. Here we activate RIG-I with synthetic RNA agonists (3pRNA) to induce resistance to RSV infection in vitro and in vivo. In vitro, pre-treatment of human, mouse and ferret airway cell lines with RIG-I agonist prior to RSV exposure inhibited virus infection and replication. Moreover, a single intravenous injection of 3pRNA one day prior to RSV infection resulted in potent inhibition of virus replication in the lungs of mice and ferrets, but not in nasal tissues. These studies provide evidence that RIG-I agonists represent a promising antiviral drug for RSV prophylaxis.

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Section: Discussionmentioning

confidence: 99%

Retinoic Acid–Inducible Gene I Activation Inhibits Human Respiratory Syncytial Virus Replication in Mammalian Cells and in Mouse and Ferret Models of Infection

Schwab

Farrukee

Eléouët

et al. 2022

The Journal of Infectious Diseases

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“…51,60 The RLR family comprises of RIG-I, melanoma differentiation association protein 5 (MDA-5), and laboratory of genetics and physiology 2 (LGP2). 60 RIG-I is activated by double stranded RNA sequences containing 5′-diphosphate (5′-ppRNA) or triphosphates (5′-ppp RNA) [52][53][54][61][62][63] while MDA5 is activated by polyinosine-polycytidylic acid ( poly(I:C)). 51 Recognition of these viral RNAs by RIG-I and MDA5 results in the activation of nuclear factor kappa-light-chain enhancer of B cells (NF-κB) and interferon regulator factor 3 (IRF3) to produce type I and III interferons and other pro-inflammatory cytokines.…”

Section: Reviewmentioning

confidence: 99%

Immunostimulatory biomaterials to boost tumor immunogenicity

et al. 2020

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“…110 Therefore, targeted nanoparticle delivery of bifunctional RIG-I agonists has been investigated. 111 It has been indicated that lipid calcium phosphate nanoparticles encapsulating dual-therapeutic 5 0 ppp dsRNA (activation of RIG-I as well as silencing of Bcl2) allowed strong induction of levels of pro-inflammatory Th1 cytokines, further increasing the proportions of CD8 + T cells over regulatory T cells, M1 over M2 macrophages, and decreased levels of immunosuppressive B regulatory and plasma cells in the tumor microenvironment, which provide a promising immunotherapy approach for pancreatic cancer. 112 Riboxxim is 100 bp dsRNA with 5 0 triphosphate ends that can activate both TLR3 and RIG-I signaling.…”

Section: Nanoparticles Targeting Rlr Signaling Pathwaysmentioning

confidence: 99%