RNA interference-based therapy and its delivery systems

Chen, Xiuhui; Mangala, Lingegowda S.; Rodríguez-Aguayo, Cristian; Kong, Xianchao; López-Berestein, Gabriel; Sood, Anil K.

doi:10.1007/s10555-017-9717-6

Cited by 241 publications

(169 citation statements)

References 197 publications

(198 reference statements)

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“…In addition, ILK expression levels positively correlate with the efficacy of Cpd22 in leukemia [29]. While siRNAs have high specificity in a sequence specific manner, small-molecule inhibitors can act over multiple targets [30]. These observations could explain in part the fact that the viability of both cisplatin-resistant and cisplatin-sensitive cells was reduced upon Cpd22 treatment.…”

Section: Discussionmentioning

confidence: 99%

Downstream Effectors of ILK in Cisplatin-Resistant Ovarian Cancer

Reyes-González

Quiñones-Díaz

Santana

et al. 2020

Cancers

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Despite good responses to first-line treatment with platinum-based combination chemotherapy, most ovarian cancer patients will relapse and eventually develop platinum-resistant disease with poor prognosis. Although reports suggest that integrin-linked kinase (ILK) is a potential target for ovarian cancer treatment, identification of ILK downstream effectors has not been fully explored. The purpose of this study was to investigate the molecular and biological effects of targeting ILK in cisplatin-resistant ovarian cancer. Western blot analysis showed that phosphorylation levels of ILK were higher in cisplatin-resistant compared with cisplatin-sensitive ovarian cancer cells. Further immunohistochemical analysis of ovarian cancer patient samples showed a significant increase in phosphorylated ILK levels in the tumor tissue when compared to normal ovarian epithelium. Targeting ILK by small-interfering RNA (siRNA) treatment reduced cisplatin-resistant cell growth and invasion ability, and increased apoptosis. Differential gene expression analysis by RNA sequencing (RNA-Seq) upon ILK-siRNA transfection followed by Ingenuity Pathway Analysis (IPA) and survival analysis using the Kaplan–Meier plotter database identified multiple target genes involved in cell growth, apoptosis, invasion, and metastasis, including several non-coding RNAs. Taken together, results from this study support ILK as an attractive target for ovarian cancer and provide potential ILK downstream effectors with prognostic and therapeutic value.

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Section: Discussionmentioning

confidence: 99%

Downstream Effectors of ILK in Cisplatin-Resistant Ovarian Cancer

Reyes-González

Quiñones-Díaz

Santana

et al. 2020

Cancers

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“…For dsRNA to pose a significant risk to human health in a sequence-specific manner is considered less likely, as a dsRNA would need to be translocated inside a cell rather than to receptors on its surface. The inability to successfully develop RNAi-based therapies indicates the magnitude of the delivery problem (Chen et al, 2018). Instability of non-coding RNAs in biological fluids due to the abundance of endogenous nucleases, and subsequent removal via the kidneys, along with inabilities to cross vascular and cellular barriers are cited as key constraints (Chen et al, 2018).…”

Section: Risks To Human Healthmentioning

confidence: 99%

“…The inability to successfully develop RNAi-based therapies indicates the magnitude of the delivery problem (Chen et al, 2018). Instability of non-coding RNAs in biological fluids due to the abundance of endogenous nucleases, and subsequent removal via the kidneys, along with inabilities to cross vascular and cellular barriers are cited as key constraints (Chen et al, 2018). Environmental dsRNA without specific protective measures would be similarly affected.…”

Section: Risks To Human Healthmentioning

confidence: 99%

A Perspective on RNAi-Based Biopesticides

et al. 2020

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“…Table 1. siRNA-based clinical trials using lipidic and polymeric vectors for cancer therapy [12,13].…”

Section: Introductionmentioning

confidence: 99%

Applications of Lipidic and Polymeric Nanoparticles for siRNA Delivery

Şenel¹,

Büyükköroğlu²

2019

Antisense Therapy

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The antisense technology that emerged with the discovery of RNA interference nearly 20 years ago has gained a significant place in gene therapy. siRNA, one of two important components of RNA interference, efficiently downregulates gene expression in human cells, so it has the potential to eradicate disease. siRNA delivery systems, which can be applied both systemically and locally in different diseases, have gained significant importance. Naked small RNAs can be delivered directly to cells, but because of their instability, exposure to enzyme degradation, and difficulties in reaching/entering the target cell or tissue in blood stream, these initiatives are failing. For this reason, the method of delivery or encapsulation of siRNA is usually required. Various nanoparticles, nanocapsules, emulsions, micelle systems, metal ion nanoparticles, and nanoconjugates have been used for siRNA delivery. In these transport systems, lipidic and polymeric systems are very attractive due to their advantages such as being biodegradable and biocompatible, safety, being able to electrostatically bind to RNA, long-term stability, well-illuminated structure and features, simple and easy production, etc. Issues such as particle size, zeta potential, and stability of siRNA-loaded system should be taken into consideration in the development of siRNA delivery systems.

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RNA interference-based therapy and its delivery systems

Cited by 241 publications

References 197 publications

Downstream Effectors of ILK in Cisplatin-Resistant Ovarian Cancer

Downstream Effectors of ILK in Cisplatin-Resistant Ovarian Cancer

A Perspective on RNAi-Based Biopesticides

Applications of Lipidic and Polymeric Nanoparticles for siRNA Delivery

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