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

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...

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Published inChemistry : a European journal Vol. 26; no. 61; pp. 14002 - 14010
Main Authors Zhang, Jinhao, Jing, Nannan, Fan, Xinli, Tang, Xinjing
Format Journal Article
LanguageEnglish
Published Germany Wiley Subscription Services, Inc 02.11.2020
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Abstract 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.
AbstractList 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.
Abstract 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.
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.
Author Zhang, Jinhao
Fan, Xinli
Jing, Nannan
Tang, Xinjing
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Keywords host-guest systems
photoactivation
oligonucleotides
RNA
gene regulation
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Snippet RNA interference is an essential and powerful tool for targeting and verifying specific gene functions. Conditional control of small interfering RNA (siRNA)...
Abstract RNA interference is an essential and powerful tool for targeting and verifying specific gene functions. Conditional control of small interfering RNA...
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SubjectTerms 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
Title Photoregulation of Gene Expression with Amantadine‐Modified Caged siRNAs through Host–Guest Interactions
URI https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fchem.202003084
https://www.ncbi.nlm.nih.gov/pubmed/32678486
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Volume 26
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