Targeted siRNA delivery using aptamer‐siRNA chimeras and aptamer‐conjugated nanoparticles

Sivakumar, P.; Kim, Sumin; Kang, Han Chang; Shim, Min Suk

doi:10.1002/wnan.1543

Cited by 35 publications

(21 citation statements)

References 111 publications

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“…ShRNA technology has obvious advantages over siRNA technology in that optimized shRNA constructs possess high potency and sustainable effects using low copy numbers and eliminates off‐target effects, which has been demonstrated in multiple studies . Recently, shRNA technology has been highly appreciated and attracted growing attention, and a new research paradigm for clinical gene therapy was built based on this technology . In this study, shRNA interference successfully and effectively block the expression of Piezo1 at the gene level, suggesting an advantage over the inhibitor GsMTx4.…”

Section: Discussionmentioning

confidence: 75%

Study on the mechanism of excessive apoptosis of nucleus pulposus cells induced by shRNA‐Piezo1 under abnormal mechanical stretch stress

Yang

Zhou

Wang

et al. 2018

J of Cellular Biochemistry

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Objective: The aim of the study was to explore the mechanism of excessive apoptosis of nucleus pulposus cells induced by short hairpin RNA (shRNA) Piezo type mechanosensitive ion channel component 1 (Piezo1) under abnormal mechanical stretch stress. Methods:In vitro mechanical stretch stress model of nucleus pulposus cells in vitro was established, in which the expression of Piezo1 was interfered by transfection of shRNA-Piezo1 interfering vector. Both messenger RNA and protein level of Piezo1 were measured by reverse-transcription polymerase chain reaction and Western blot analysis, respectively. Cytoplasmic Ca 2+ was detected by Fluo3-AM kit, and changes of mitochondrial membrane potential in cells were detected using Cell Meter Assay kit. Finally, the apoptosis was evaluated with annexin V-fluorescein isothiocyanate kit.Results: The highest transfection efficiency of lentivirus titer was 1 × 10 TU/mL and the nucleus pulposus cells were transfected with plural multiplicity of infection = 50.Homo-3201 sequence exhibited the most effective silencing effect and was used in subsequent experiments as the default sequence of shRNA-Piezo1. The calcium content in the cytoplasm of the tension stress group increased significantly compared with that in the blank control group (q = 3.773; P < 0.05). The level of cytosolic calcium in shRNA-interference group was significantly lower than that in stretch stress group (q = 5.159; P < 0.05). Stretch stress treatment resulted in an elevated ratio of mitochondrial membrane potential turnover as opposed to blank control group (q = 4.332; P < 0.05), while shRNA-interference group showed smaller ratio of mitochondrial membrane potential turnover than that in stretch stress group (q = 4.974; P < 0.05). Similar results were also observed in apoptosis rate analysis (q = 3.175; P < 0.05). Conclusion: ShRNA-Piezo1 can protect cells by reducing the level of intracellular Ca 2+ and the change of mitochondrial membrane potential. Study on the mechanism of excessive apoptosis of nucleus pulposus cells induced by shRNA-Piezo1 under abnormal mechanical stretch stress.

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Section: Discussionmentioning

confidence: 75%

Study on the mechanism of excessive apoptosis of nucleus pulposus cells induced by shRNA‐Piezo1 under abnormal mechanical stretch stress

Yang

Zhou

Wang

et al. 2018

J of Cellular Biochemistry

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“…Aptamers are also used for targeted delivery of drugs and other genetic elements, such as siRNAs, to cells (18)(19)(20). siRNAs are reliable gene knockdown tools.…”

Section: Rationalementioning

confidence: 99%

An aptamer/ siRNA Chimera against The SARS-CoV-2: A Dual Therapeutic Strategy for The Virus Neutralizing and RNA Interfering

Khanali¹,

Azangou‐Khyavy²,

Asaadi³

et al. 2020

Preprint

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During the ongoing COVID-19 pandemic, besides the vaccines, there is an urgent need for the development of effective therapeutics. Although significant efforts have been made to develop such therapies, there are currently no approved treatments for COVID-19. One of the potential therapeutic targets is the spike (S) protein of SARS-CoV-2, which mediates viral entry into host cells. It has been shown that targeting S protein could neutralize viruses and hinder their binding to the cells. Among known viral neutralizing agents, aptamers’ potential in neutralizing the SARS-Cov-2 virus has not yet been revealed. In addition, aptamers could also be used for targeted delivery of drugs and other genetic elements, such as siRNAs, to the cells. Small interfering RNAs (siRNAs) are reliable tools for gene knockdown via RNA degradation. siRNAs have been implemented previously against some viruses, including SARS-CoV, to target its genome. Recently, potential siRNA sequences and their targets in the SARS-CoV-2 genome have been reported, and the efficiency of siRNAs in inhibiting SARS-CoV-2 infection is being revealed. An alternative antiviral approach we propose here relies on an aptamer-siRNA-based system for the treatment of COVID-19. These aptamers could neutralize viruses by hindering their receptor-mediated endocytosis, and siRNAs could suppress the expression of viral genes and halt various aspects of its pathogenesis whenever the aptamers fail to neutralize the virus.

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“…There is the possibility of target specificity, RNAi efficacy, and stability of siRNA-aptamers chimeras being affected by chemical modifications. Therefore, it is crucial to find an optimal alternative for each siRNA aptamers chimera to maximize its therapeutic efficacy [38].…”

Section: Aptamer In the Delivery Of Therapeutic Nanoparticles Containmentioning

confidence: 99%

“…Furthermore, it has been shown that PEG formulation reduces immune responses in vivo [41]. The thermal stability of siRNA is another parameter to be considered in gene silencing activity when it is conjugated to aptamers [38]. In this context, the computational modeling has been used to guide RNA aptamer truncations, maintaining their functionality, and preventing and minimizing therapy challenges using siRNA.…”

Section: Aptamer In the Delivery Of Therapeutic Nanoparticles Containmentioning

confidence: 99%

Aptamers as Delivery Agents of siRNA and Chimeric Formulations for the Treatment of Cancer

Almeida

et al. 2019

Pharmaceutics

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Both aptamers and siRNA technologies have now reached maturity, and both have been validated with a product in the market. However, although pegaptanib reached the market some time ago, there has been a slow process for new aptamers to follow. Today, some 40 aptamers are in the market, but many in combination with siRNAs, in the form of specific delivery agents. This combination offers the potential to explore the high affinity and specificity of aptamers, the silencing power of siRNA, and, at times, the cytotoxicity of chemotherapy molecules in powerful combinations that promise to delivery new and potent therapies. In this review, we report new developments in the field, following up from our previous work, more specifically on the use of aptamers as delivery agents of siRNA in nanoparticle formulations, alone or in combination with chemotherapy, for the treatment of cancer.

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Targeted siRNA delivery using aptamer‐siRNA chimeras and aptamer‐conjugated nanoparticles

Cited by 35 publications

References 111 publications

Study on the mechanism of excessive apoptosis of nucleus pulposus cells induced by shRNA‐Piezo1 under abnormal mechanical stretch stress

Study on the mechanism of excessive apoptosis of nucleus pulposus cells induced by shRNA‐Piezo1 under abnormal mechanical stretch stress

An aptamer/ siRNA Chimera against The SARS-CoV-2: A Dual Therapeutic Strategy for The Virus Neutralizing and RNA Interfering

Aptamers as Delivery Agents of siRNA and Chimeric Formulations for the Treatment of Cancer

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