Abstract
We designed and synthesized caged siRNAs with photolabile linker and single cRGD peptide modifications for the photoregulation of gene expression. Photolabile linker and cRGD were inserted at 5′ terminus of siRNAs to obtain cRGD-modified caged siRNAs. All these caged siRNAs could be activated through light activation to release the native siRNAs and further achieve the photoregulation of gene silencing of two exogenous reporter genes (firefly luciferase and green fluorescent protein, GFP) and one endogenous gene (the mitosis motor protein, Eg5). The intracellular distribution and cellular uptake pathways of these caged siRNAs were also investigated. Tumor-bearing mice were further used to demonstrate the photoregulation of gene silencing with cRGD-modified caged siRNAs in vivo. Overall, the data support the use of this new generation of caged siRNAs in cancer therapy.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T (2001) Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411:494–498
Roberts TC, Ezzat K, EL Andaloussi S, Weinberg MS (2016) Synthetic SiRNA delivery: progress and prospects. In: Shum K, Rossi J (eds) SiRNA delivery methods: methods and protocols. Springer New York, New York, NY, pp 291–310. https://doi.org/10.1007/978-1-4939-3112-5_23
Broering R, Real CI, John MJ, Jahn-Hofmann K, Ickenstein LM, Kleinehr K, Paul A, Gibbert K, Dittmer U, Gerken G, Schlaak JF (2013) Chemical modifications on siRNAs avoid toll-like-receptor-mediated activation of the hepatic immune system in vivo and in vitro. Int Immunol 26:35–46
Tluk S, Jurk M, Forsbach A, Weeratna R, Samulowitz U, Krieg AM, Bauer S, Vollmer J (2009) Sequences derived from self-RNA containing certain natural modifications act as suppressors of RNA-mediated inflammatory immune responses. Int Immunol 21:607–619
Chen C, Yang Z, Tang X (2018) Chemical modifications of nucleic acid drugs and their delivery systems for gene-based therapy. Med Res Rev 38:829–869
Ku SH, Jo SD, Lee YK, Kim K, Kim SH (2016) Chemical and structural modifications of RNAi therapeutics. Adv Drug Deliv Rev 104:16–28
Debart F, Dupouy C, Vasseur J-J (2018) Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing. Beilstein J Org Chem 14:436–469
Casey JP, Blidner RA, Monroe WT (2009) Caged siRNAs for spatiotemporal control of gene silencing. Mol Pharm 6:669–685
Shah S, Rangarajan S, Friedman SH (2005) Light-activated RNA interference. Angew Chem Int Ed 44:1328–1332
Jain PK, Shah S, Friedman SH (2011) Patterning of gene expression using new photolabile groups applied to light activated RNAi. J Am Chem Soc 133:440–446
Yu L, Liang D, Chen C, Tang X (2018) Caged siRNAs with single cRGD modification for photoregulation of exogenous and endogenous gene expression in cells and mice. Biomacromolecules 19:2526–2534
Ji Y, Yang J, Wu L, Yu L, Tang X (2016) Photochemical regulation of gene expression using caged siRNAs with single terminal vitamin E modification. Angew Chem Int Ed 55:2152–2156
Yu L, Jing N, Yang Z, Zhang L, Tang X (2018) Caged siRNAs with single folic acid modification of antisense RNA for photomodulation of exogenous and endogenous gene expression in cells. Org Biomol Chem 16:7029–7035
Zhang L, Chen C, Fan X, Tang X (2018) Photomodulating gene expression by using caged siRNAs with single-aptamer modification. Chembiochem 19:1259–1263
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2020 Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Yu, L., Liang, D., Jing, N., Chen, C., Tang, X. (2020). Synthesis and Evaluation of Caged siRNAs with Single cRGD Modification for Photoregulating RNA Interference. In: Sioud, M. (eds) RNA Interference and CRISPR Technologies. Methods in Molecular Biology, vol 2115. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0290-4_8
Download citation
DOI: https://doi.org/10.1007/978-1-0716-0290-4_8
Published:
Publisher Name: Humana, New York, NY
Print ISBN: 978-1-0716-0289-8
Online ISBN: 978-1-0716-0290-4
eBook Packages: Springer Protocols