Dataset Information

SEVs^RVG selectively delivers antiviral siRNA to fetus brain, inhibits ZIKV infection and mitigates ZIKV-induced microcephaly in mouse model.

ABSTRACT: Zika virus (ZIKV), a flavivirus associated with neurological disorders, constitutes a global health threat. During pregnancy, ZIKV traverses the placenta and causes congenital disease such as microcephaly and Guillain-Barré syndrome in newborns. To develop a specific antiviral therapy against ZIKV-induced microcephaly that could cross placental and blood-brain barriers, we designed targeted small extracellular vesicles (sEVs) encapsulating antiviral siRNA (small interfering RNA) to inhibit ZIKV. The neuro-specific targeting was achieved by engineering EVs membrane protein lamp2b fused with a neuron-specific rabies virus glycoprotein derived peptide (RVG). Intravenous administration of the RVG-engineered sEVs loaded with siRNA (ZIKV-specific siRNA) protected pregnant AG6 mice against vertical transmission of ZIKV. Particularly, sEVs^RVG-siRNA traversed placental and blood-brain barriers and suppressed ZIKV infection in fetal brains. Moreover, sEVs^RVG-siRNA alleviated the neuroinflammation and neurological damage caused by ZIKV in the fetal mouse model. In general, we developed a sEVs-based targeted system of antiviral therapy for brain and fetal brain infections.

SUBMITTER: Zhang R

PROVIDER: S-EPMC9092305 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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sEVs<sup>RVG</sup> selectively delivers antiviral siRNA to fetus brain, inhibits ZIKV infection and mitigates ZIKV-induced microcephaly in mouse model.

Zhang Rui R Fu Yuxuan Y Cheng Min M Ma Wenyuan W Zheng Nan N Wang Yongxiang Y Wu Zhiwei Z

Molecular therapy : the journal of the American Society of Gene Therapy 20211110 5

Zika virus (ZIKV), a flavivirus associated with neurological disorders, constitutes a global health threat. During pregnancy, ZIKV traverses the placenta and causes congenital disease such as microcephaly and Guillain-Barré syndrome in newborns. To develop a specific antiviral therapy against ZIKV-induced microcephaly that could cross placental and blood-brain barriers, we designed targeted small extracellular vesicles (sEVs) encapsulating antiviral siRNA (small interfering RNA) to inhibit ZIKV. ...[more]

PMID: 34762817

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Project description:Background Total liquid ventilation (TLV) has been shown to prevent neurological damage though ultrafast cooling in animal models of cardiac arrest. We investigated whether its neuroprotective effect could be explained by mitigation of early inflammatory events. Methods and Results Rabbits were submitted to 10 minutes of ventricular fibrillation. After resuscitation, they underwent normothermic follow-up (control) or ultrafast cooling by TLV and hypothermia maintenance for 3 hours (TLV). Immune response, survival, and neurological dysfunction were assessed for 3 days. TLV improved neurological recovery and reduced cerebral lesions and leukocyte infiltration as compared with control (eg, neurological dysfunction score=34±6 versus 66±6% at day 1, respectively). TLV also significantly reduced interleukin-6 blood levels during the hypothermic episode (298±303 versus 991±471 pg/mL in TLV versus control at 3 hours after resuscitation, respectively), but not after rewarming (752±563 versus 741±219 pg/mL in TLV versus control at 6 hours after resuscitation, respectively). In vitro assays confirmed the high temperature sensitivity of interleukin-6 secretion. Conversely, TLV did not modify circulating high-mobility group box 1 levels or immune cell recruitment into the peripheral circulation. The link between interleukin-6 early transcripts (<8 hours) and neurological outcome in a subpopulation of the previously described Epo-ACR-02 (High Dose of Erythropoietin Analogue After Cardiac Arrest) trial confirmed the importance of this cytokine at the early stages as compared with delayed stages (>8 hours). Conclusions The neuroprotective effect of hypothermic TLV was associated with a mitigation of humoral interleukin-6 response. A temperature-dependent attenuation of immune cell reactivity during the early phase of the post-cardiac arrest syndrome could explain the potent effect of rapid hypothermia. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00999583.

Dataset Information

SEVs^RVG selectively delivers antiviral siRNA to fetus brain, inhibits ZIKV infection and mitigates ZIKV-induced microcephaly in mouse model.

Publications

sEVs<sup>RVG</sup> selectively delivers antiviral siRNA to fetus brain, inhibits ZIKV infection and mitigates ZIKV-induced microcephaly in mouse model.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

SEVsRVG selectively delivers antiviral siRNA to fetus brain, inhibits ZIKV infection and mitigates ZIKV-induced microcephaly in mouse model.

Publications

sEVs<sup>RVG</sup> selectively delivers antiviral siRNA to fetus brain, inhibits ZIKV infection and mitigates ZIKV-induced microcephaly in mouse model.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

SEVs^RVG selectively delivers antiviral siRNA to fetus brain, inhibits ZIKV infection and mitigates ZIKV-induced microcephaly in mouse model.