Reversible control of RNA interference by siRNAzos

Hammill, Matthew L.; Islam, Golam; Desaulniers, Jean-Paul

doi:10.1039/c9ob02509j

Cited by 20 publications

(25 citation statements)

References 21 publications

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“…Conversely exposure to visible light reactivates the siRNAzo and the genes are silenced in real time. Additionally, this process is reversible, and can be performed up to twice in the same experiment, as we demonstrated in one of our recent papers (Hammill, Islam, & Desaulniers, 2020a) by exposure to UV light, then visible, then UV light again to show that it is not being degraded or metabolized during this time with no loss of functionality. This opens the door for longer term experiments, when the siRNAzo could be inactivated for several days, and then reactivated at a chosen time.…”

Section: Background Informationmentioning

confidence: 70%

“…These protocols were used to develop a robust and modifiable system, on which we have published several papers (cited above); the second most recent of which (Hammill et al., 2020a) allowed us to push our technology to the next level by inactivating the siRNA with UV light, and then keeping it off for 24 hr (Fig. 3).…”

Section: Commentarymentioning

confidence: 99%

“…These unique and modular properties allow azobenzene to be used in many applications, including its incorporation into oligonucleotides (Hammill et. al., 2017;Hammill et al" 2018;Hammill & Desaulniers, 2020;Hammill et al, 2020aHammill et al, , 2020b.…”

Section: Introductionmentioning

confidence: 99%

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Controlling Gene‐Silencing with Azobenzene‐Containing siRNAs (siRNAzos)

Hammill

Islam

Desaulniers

2020

CP Nucleic Acid Chemistry

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This article contains the detailed biophysical characterization, biological testing, and photo-switching protocols of azobenzene containing siRNAs (siRNAzos), which have photoswitchable properties that can be controlled with light. First, the siRNAzos are characterized by annealing the sense and anti-sense strands together and then measuring the circular dichroism (CD) profile, and the melting temperatures (T m) of the duplexes. Second, the biological testing of the siRNAzos in cell culture is done to determine their gene silencing efficacy. Finally, their gene-silencing activities are measured after exposure to ultraviolet (UV) light in order to inactivate the siRNAzo, and then broadband visible light, which reactivates the siRNAzo. This inactivation/reactivation protocol can be done in real time, and is reversible and robust and can be performed multiple times on the same sample if desired.

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Section: Background Informationmentioning

confidence: 70%

Section: Commentarymentioning

confidence: 99%

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Controlling Gene‐Silencing with Azobenzene‐Containing siRNAs (siRNAzos)

Hammill

Islam

Desaulniers

2020

CP Nucleic Acid Chemistry

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“…Azobenzene under visible light irradiation remains in trans ‐isomeric state and keeps the siRNA functional. Under UV light irradiation azobenzene switches to cis ‐isomer causing reversible inactivation of siRNAzo [239c,248] . Reversible control of RNAi under different disease condition can be a modern paradigm for application of RNAi therapeutics.…”

Section: Discussionmentioning

confidence: 99%

Emerging Approaches for Enabling RNAi Therapeutics

Mallick

Tripathi

Mishra

et al. 2022

Chemistry An Asian Journal

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RNA interference (RNAi) is a primitive evolutionary mechanism developed to escape incorporation of foreign genetic material. siRNA has been instrumental in achieving the therapeutic potential of RNAi by theoretically silencing any gene of interest in a reversible and sequence-specific manner. Extrinsically administered siRNA generally needs a delivery vehicle to span across different physiological barriers and load into the RISC complex in the cytoplasm in its functional form to show its efficacy. This review discusses the designing principles and examples of different classes of delivery vehicles that have proved to be efficient in RNAi therapeutics. We also briefly discuss the role of RNAi therapeutics in genetic and rare diseases, epigenetic modifications, immunomodulation and combination modality to inch closer in creating a personalized therapy for metastatic cancer. At the end, we present, strategies and look into the opportunities to develop efficient delivery vehicles for RNAi which can be translated into clinics.

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“…17H). [138][139][140] A related, tetra ortho-chlorinated azobenzenecontaining siRNAs (Cl-siRNAzos) shied the trans to cis conversion wavelength to 660 nm (red-shi) and was applied in cell culture gene inactivation studies (Fig. 17H).…”

Section: Azobenzenementioning

confidence: 99%