Photoregulation of Gene Expression with Amantadine‐Modified Caged siRNAs through Host–Guest Interactions

• Published in: Chemistry : a European journal Vol. 26; no. 61; pp. 14002 - 14010
• Main Authors: Zhang, Jinhao, Jing, Nannan, Fan, Xinli, Tang, Xinjing
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 02.11.2020
• Subjects: Amantadine; Amantadine - chemistry; Antisense RNA; Chemistry; Cyclodextrin; Cyclodextrins; Gene expression; Gene Expression - radiation effects; gene regulation; Gene silencing; Gene Silencing - radiation effects; host–guest systems; oligonucleotides; photoactivation; Photochemical Processes; Ribonucleic acid; RNA; RNA Interference; RNA processing; RNA, Small Interfering - chemistry; RNA, Small Interfering - genetics; RNA-mediated interference; siRNA; host-guest systems; photoactivation; oligonucleotides; RNA; gene regulation
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.202003084

RNA interference is an essential and powerful tool for targeting and verifying specific gene functions. Conditional control of small interfering RNA (siRNA) activity, especially using light activation, is a potential method for regulating target gene expression and functions. In this study, a series of photolabile siRNAs with amantadine modification have been rationally designed and developed through host–guest interactions between amantadine and β‐cyclodextrin derivatives to enhance the blocking effect of siRNA binding and/or RNA‐induced silencing complex processing. These caged siRNAs with amantadine modification at the 5′ end of antisense‐strand RNA were efficiently inactivated through the host–guest interactions between amantadine and β‐cyclodextrin. Photomodulation of the gene silencing activity of these amantadine‐modified caged siRNAs targeting both exogenous and endogenous genes was successfully achieved, which indicates that host–guest interactions could be a new strategy for developing new caged siRNAs for gene photoregulation with low leaking activity. A new type of caging strategy involving host–guest interactions has been developed by using amantadine‐modified caged siRNAs (see figure). The host–guest interactions between amantadine and β‐cyclodextrin derivatives greatly enhanced the blocking effect of RNA‐induced silencing complex formation and/or processing. The photoregulation of both exogenous and endogenous gene silencing was successfully achieved with low leaking activity.