Abstract:Gene silencing through RNA interference (RNAi) has emerged as a potential strategy in manipulating cancer causing genes by complementary base-pairing mechanism. Small interfering RNA (siRNA) is an important RNAi tool that has found significant application in cancer therapy. However due to lack of stability, poor cellular uptake and high probability of loss-of-function due to degradation, siRNA therapeutic strategies seek safe and efficient delivery vehicles for in vivo applications. The current review discusse… Show more
“…The expression of RAN was reduced significantly in both cases, but encapsulated shRNA-1 was found to be more effective than shRNA-4 as evident from the percentage of reduction of RAN expression. These results demonstrate RNA interference [ 36 ] and verifies the specificity of the shRNA variants used in this work towards RAN . Fig.…”
Section: Resultssupporting
confidence: 70%
“…The expression of RAN was reduced significantly in both cases, but encapsulated shRNA-1 was found to be more effective than shRNA-4 as evident from the percentage of reduction of RAN expression. These results demonstrate RNA interference [36] and verifies the specificity of the shRNA variants used in this work towards RAN .Fig. 6qRT-PCR for RAN gene expression after 24 and 48 h transfection of PLGA-shRNA-1 NP and PLGA-shRNA-4, where cells were transfected with 2.0 μg ml −1 shRNA-1 and 2.0 μg ml −1 shRNA-4.…”
BackgroundOverexpression of the RAN GTP (RAN) gene has been shown to be linked to metastatic activity of MDA-MB231 human breast cancer cells by increasing Ras/MEK/ERK and PI3K/Akt/mTORC1 signalling. The aim of this study was to investigate the potential of polymeric nanoparticles to deliver two novel shRNA sequences, targeted against the RAN gene, to MDA-MB231 cells grown in culture and to assess their effects in a range of biological assays.MethodsBiodegradable PLGA nanoparticles, loaded with shRNA-1 and shRNA-4, were fabricated using a double emulsion solvent evaporation technique and characterised for size, zeta potential and polydispersity index before testing on the MDA-MB231 cell line in a range of assays including cell viability, migration, invasion and gene knock down.ResultsshRNA-loaded nanoparticles were successfully fabricated and delivered to MDA-MB231 cells in culture, where they effectively released their payload, causing a decrease in both cell invasion and cell migration by knocking down RAN gene expression.ConclusionResults indicate the anti-RAN shRNA-loaded nanoparticles deliver and release biological payload to MDA-MB231 cells in culture. This works paves the way for further investigations into the possible use of anti-RAN shRNA-loaded NP formulations for the treatment of breast cancer in vivo.
“…The expression of RAN was reduced significantly in both cases, but encapsulated shRNA-1 was found to be more effective than shRNA-4 as evident from the percentage of reduction of RAN expression. These results demonstrate RNA interference [ 36 ] and verifies the specificity of the shRNA variants used in this work towards RAN . Fig.…”
Section: Resultssupporting
confidence: 70%
“…The expression of RAN was reduced significantly in both cases, but encapsulated shRNA-1 was found to be more effective than shRNA-4 as evident from the percentage of reduction of RAN expression. These results demonstrate RNA interference [36] and verifies the specificity of the shRNA variants used in this work towards RAN .Fig. 6qRT-PCR for RAN gene expression after 24 and 48 h transfection of PLGA-shRNA-1 NP and PLGA-shRNA-4, where cells were transfected with 2.0 μg ml −1 shRNA-1 and 2.0 μg ml −1 shRNA-4.…”
BackgroundOverexpression of the RAN GTP (RAN) gene has been shown to be linked to metastatic activity of MDA-MB231 human breast cancer cells by increasing Ras/MEK/ERK and PI3K/Akt/mTORC1 signalling. The aim of this study was to investigate the potential of polymeric nanoparticles to deliver two novel shRNA sequences, targeted against the RAN gene, to MDA-MB231 cells grown in culture and to assess their effects in a range of biological assays.MethodsBiodegradable PLGA nanoparticles, loaded with shRNA-1 and shRNA-4, were fabricated using a double emulsion solvent evaporation technique and characterised for size, zeta potential and polydispersity index before testing on the MDA-MB231 cell line in a range of assays including cell viability, migration, invasion and gene knock down.ResultsshRNA-loaded nanoparticles were successfully fabricated and delivered to MDA-MB231 cells in culture, where they effectively released their payload, causing a decrease in both cell invasion and cell migration by knocking down RAN gene expression.ConclusionResults indicate the anti-RAN shRNA-loaded nanoparticles deliver and release biological payload to MDA-MB231 cells in culture. This works paves the way for further investigations into the possible use of anti-RAN shRNA-loaded NP formulations for the treatment of breast cancer in vivo.
“…Further, the ongoing clinical trials using encapsulated siRNA as a drug against cancer strengthens the anticancer potential of siRNA (Table 2). 99,100 4 | SHORT HAIRPIN RNA AND ITS DELIVERY…”
Background: Drug delivery system is a common practice in cancer treatment. RNA interference-mediated post-transcriptional gene silencing holds promise as an approach to knockdown in the expression of target genes responsible for cancer cell growth and metastasis. RNA interference (RNAi) can be achieved by delivering small interfering RNA (siRNA) and short hairpin RNA (shRNA) to target cells. Since neither interfering RNAs can be delivered in naked form due to poor stability, an efficient delivery system is required that protects, guides, and delivers the siRNA and shRNA to target cells as part of cancer therapy (chemotherapy). Recent findings: In this review, a discussion is presented about the different types of drug delivery system used to deliver siRNA and shRNA, together with an overview of the potential benefits associated with this sophisticated biomolecular therapy. Improved understanding of the different approaches used in nanoparticle (NP) fabrication, along with an enhanced appreciation of the biochemical properties of siRNA/ shRNA, will assist in developing improved drug delivery strategies in basic and clinical research. Conclusion: These novel delivery techniques are able to solve the problems that form an inevitable part of delivering genes in more efficient manner and as part of more effective treatment protocols. The present review concludes that the nanoparticulate RNA delivery system has great possibility for cancer treatment along with several other proposed methods. Several NPs or nanocarriers are already in use, but the methods proposed here could fulfill the missing gap in cancer research. It is the future technology, which unravels the mystery of resolving genomic diseases that is, especially genomic instability and its signaling cascades.
“…or inorganic nanoparticles (carbon nanotubes, gold and mesoporous silica nanoparticles), have shown multiple advantages concerning RNAi delivery [ 31 ]. In fact, nanoparticles have received considerable attention due to their ability to protect RNAi molecules from enzymatic degradation and their capacity to be associated with specific peptides, increasing their selectivity for tumor cells [ 32 , 33 ]. In addition, chemical modifications involving sugar and phosphate and chemical structure modifications in the oligonucleotide backbone of RNAi have been proven to be efficient as they considerably reduce toxicity, off-target effects and degradation by nucleases [ 34 , 35 ].…”
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy with one of the highest mortality rates among solid cancers. It develops almost exclusively in the background of chronic liver inflammation, which can be caused by viral hepatitis, chronic alcohol consumption or an unhealthy diet. Chronic inflammation deregulates the innate and adaptive immune responses that contribute to the proliferation, survival and migration of tumor cells. The continuous communication between the tumor and its microenvironment components serves as the overriding force of the tumor against the body’s defenses. The importance of this crosstalk between the tumor microenvironment and immune cells in the process of hepatocarcinogenesis has been shown, and therapeutic strategies modulating this communication have improved the outcomes of patients with liver cancer. To target this communication, an RNA interference (RNAi)-based approach can be used, an innovative and promising strategy that can disrupt the crosstalk at the transcriptomic level. Moreover, RNAi offers the advantage of specificity in comparison to the treatments currently used for HCC in clinics. In this review, we will provide the recent data pertaining to the modulation of a tumor and its microenvironment by using RNAi and its potential for therapeutic intervention in HCC.
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