An influenza virus-inspired polymer system for the timed release of siRNA

Truong, Nghia P.; Gu, Wenyi; Prasadam, Indira; Jia, Zhongfan; Crawford, Ross; Xiao, Yin; Monteiro, Michael J.

doi:10.1038/ncomms2905

Cited by 164 publications

(180 citation statements)

References 39 publications

(48 reference statements)

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“…4,5 Nevertheless, due to poor stability of siRNA in physiological conditions and its inability to cross cellular membranes, the in vivo delivery of siRNA holds a great challenge and remains a crucial issue for its therapeutic success. 6 Many kinds of nanosized cationic delivery systems have been developed for siRNAs delivery through electrostatic interaction, such as cationic polymers [7][8][9] and cationic lipids, 10,11 among which cationic lipids are the most widely used for systemic delivery of RNAi therapeutics in vivo. However, the toxicity is still an obstacle to the application of cationic lipids in siRNA delivery.…”

Section: Introductionmentioning

confidence: 99%

Hypoxia-responsive ionizable liposome delivery siRNA for glioma therapy

Liu¹,

Zhang²,

Xie³

et al. 2017

IJN

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Here, we report the hypoxia-responsive ionizable liposomes to deliver small interference RNA (siRNA) anticancer drugs, which can selectively enhance cellular uptake of the siRNA under hypoxic and low-pH conditions to cure glioma. For this purpose, malate dehydrogenase lipid molecules were synthesized, which contain nitroimidazole groups that impart hypoxia sensitivity and specificity as hydrophobic tails, and tertiary amines as hydrophilic head groups. These malate dehydrogenase molecules, together with DSPE-PEG2000 and cholesterol, were self-assembled into O′ 1 ,O 1 -(3-(dimethylamino)propane-1,2-diyl) 16-bis(2-(2-methyl-5-nitro-1 H -imidazol-1-yl)ethyl) di(hexadecanedioate) liposomes (MLP) to encapsulate siRNA through electrostatic interaction. Our study showed that the MLP could deliver polo-like kinase 1 siRNA (siPLK1) into glioma cells and effectively enhance the cellular uptake of MLP/siPLK1 because of increased positive charges induced by hypoxia and low pH. Moreover, MLP/siPLK1 was shown to be very effective in inhibiting the growth of glioma cells both in vitro and in vivo. Therefore, the MLP is a promising siRNA delivery system for tumor therapy.

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Section: Introductionmentioning

confidence: 99%

Hypoxia-responsive ionizable liposome delivery siRNA for glioma therapy

Liu¹,

Zhang²,

Xie³

et al. 2017

IJN

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“…when siRNA give to mice either before or after virus infection, siRNA decrease influenza virus activity in the lungs (Truong et al, 2013). Sequence-specific M1 siRNA could be used to inhibit viral protein synthesis and viral replication.…”

Section: Rna Interference and Inhibition Of Virusesmentioning

confidence: 99%

RNAi and miRNA in Viral Infections and Cancers

Mollaie¹,

Monavari²,

Arabzadeh³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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“…SiRNA is performing as a component of RNAi pathway, which is one of the most important regulation's pathways for gene expression in animal cells [7][8][9]. One of the antiviral defenses in vertebrates which include variety of mechanisms to inhibit virus replication is RNA silencing pathways.…”

Section: Introductionmentioning

confidence: 99%

Antiviral Activity of Specific siRNA against Hemagglutinin and Neuraminidase of Influenza Virus H1N1 in MDCK Cell Culture

Mollaei¹

2016

MOJI

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H1N1 influenza virus causes respiratory syndrome on the upper respiratory system. Hemagglutinin (HA) and Neuraminidase (NA) proteins are the most important viral proteins that play a role in attachment and facilitates of releasing virus respectively. Short interfering RNA (siRNA) plays notable a roles in the RNA interference (RNAi) pathway and interferes the expression of specific genes with complementary nucleotide sequences by breaking down mRNA function and stopping transcription and translation. To explore shutting down HA and NA, siRNA were designed and genes of H1N1 are inhibited by siRNA molecules in MDCK cell culture.The cells were infected with virus and then treated by different concentration of siRNA. The HA, NA gene expression and the viral load were investigated by Real Time PCR between 24 to 72 hours. The cells were infected with H1N1 virus at a multiplicity of infection (MOI: 3) and then treated with different concentration of siRNA (0.5-6 nmol/L) and monitored for 72 hours post transfection. Interestingly, the viral load extremely decreased at first hours, even the viral load was not detectable after 48 hours. Three nmol/L concentration of siRNA for HA was more effective. In case of siRNA for NA, 3 nmol/L concentrations shows efficacy and also cytopathic effect (CPE) was not observed in 3 nmol/L concentrations in MDCK cells. This study suggests that siRNA against NA and HA, silenced viral genes in H1N1 influenza virus infected cells. Results showed that siRNA is an efficient tool for silencing influenza virus infection. The advantage of siRNA is the specific inhibition of mRNA which can be used for inhibition of other flu viral genes and/or other viruses.

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An influenza virus-inspired polymer system for the timed release of siRNA

Cited by 164 publications

References 39 publications

Hypoxia-responsive ionizable liposome delivery siRNA for glioma therapy

Hypoxia-responsive ionizable liposome delivery siRNA for glioma therapy

RNAi and miRNA in Viral Infections and Cancers

Antiviral Activity of Specific siRNA against Hemagglutinin and Neuraminidase of Influenza Virus H1N1 in MDCK Cell Culture

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