Efficient Targeted Delivery of Bifunctional Circular Aptamer-ASO Chimera to Suppress the SARS-CoV-2 Proliferation and Inflammation.
Gang YangShengnan ZhangWilliam SongXia BaiLing LiFatao LuoYiran ChengDiyue WangYanqun WangJiantao ChenJincun ZhaoYongyun ZhaoPublished in: Small (Weinheim an der Bergstrasse, Germany) (2023)
Inhibition of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and excessive inflammation is the current task in the prevention and treatment of corona vireus disease 2019 (COVID-19). Here, a dual-function circular aptamer-ASO chimera (circSApt-NASO) is designed to suppress SARS-CoV-2 replication and inflammation. The chemically unmodified circSApt-NASO exhibits high serum stability by artificial cyclization. It is also demonstrated that the SApt binding to spike protein enables the chimera to be efficiently delivered into the host cells expressing ACE2 along with the infection of SARS-CoV-2. Among them, the SApt potently inhibits spike-induced inflammation. The NASO targeting to silence N genes not only display robust anti-N-induced inflammatory activity, but also achieve efficient inhibition of SARS-CoV-2 replication. Overall, benefiting from the high stability of the cyclization, antispike aptamer-dependent, and viral infection-mediate targeted delivery, the circSApt-NASO displays robust potential against authentic SARS-CoV-2 and Omicron, providing a promising specific anti-inflammatory and antiproliferative reagent for therapeutic COVID-19.
Keyphrases
- sars cov
- respiratory syndrome coronavirus
- oxidative stress
- diabetic rats
- coronavirus disease
- induced apoptosis
- gold nanoparticles
- high glucose
- anti inflammatory
- gene expression
- magnetic nanoparticles
- endothelial cells
- physical activity
- dna methylation
- climate change
- angiotensin converting enzyme
- binding protein
- body mass index
- quantum dots
- drug delivery
- bioinformatics analysis
- human health