Delivery of antiviral small interfering RNA with gold nanoparticles inhibits dengue virus infection in vitro.
Dengue virus (DENV) infection in humans can cause flu-like illness, life-threatening haemorrhagic fever or even death. There is no specific anti-DENV therapeutic or approved vaccine currently available, partially due to the possibility of antibody-dependent enhancement reaction. Small interfering RNAs (siRNAs) that target specific viral genes are considered a promising therapeutic alternative against DENV infection. However, in vivo, siRNAs are vulnerable to degradation by serum nucleases and rapid renal excretion due to their small size and anionic character. To enhance siRNA delivery and stability, we complexed anti-DENV siRNAs with biocompatible gold nanoparticles (AuNPs) and tested them in vitro. We found that cationic AuNP-siRNA complexes could enter Vero cells and significantly reduce DENV serotype 2 (DENV-2) replication and infectious virion release under both pre- and post-infection conditions. In addition, RNase-treated AuNP-siRNA complexes could still inhibit DENV-2 replication, suggesting that AuNPs maintained siRNA stability. Collectively, these results demonstrated that AuNPs were able to efficiently deliver siRNAs and control infection in vitro, indicating a novel anti-DENV strategy.
Department of Biological Sciences, University of Southern Mississippi, Hattiesburg, MS 39406, USA.
Amber M
AM
Paul
Department of Chemistry and Biochemistry, University of Southern Mississippi, Hattiesburg, MS 39406, USA.
Yongliang
Y
Shi
Department of Biological Sciences, University of Southern Mississippi, Hattiesburg, MS 39406, USA.
Dhiraj
D
Acharya
Department of Biological Sciences, University of Southern Mississippi, Hattiesburg, MS 39406, USA.
Jessica R
JR
Douglas
Department of Biological Sciences, University of Southern Mississippi, Hattiesburg, MS 39406, USA.
Amanda
A
Cooley
Department of Entomology, Connecticut Agricultural Experiment Station, New Haven, CT 06504, USA.
John F
JF
Anderson
Department of Chemistry and Biochemistry, University of Southern Mississippi, Hattiesburg, MS 39406, USA.
Faqing
F
Huang
Department of Biological Sciences, University of Southern Mississippi, Hattiesburg, MS 39406, USA.
Fengwei
F
Bai
D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism*; D002522:Chlorocebus aethiops; D003716:Dengue Virus / Q000235:genetics / Q000502:physiology*; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism*; D006046:Gold / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism*; D014709:Vero Cells; D057074:Virus Release; D014779:Virus Replication
D000998:Antiviral Agents; D004337:Drug Carriers; D034741:RNA, Small Interfering; D006046:Gold