Challenges and opportunities for siRNA-based cancer treatment

Wang, Tao; Shigdar, Sarah; Shamaileh, Hadi Al; Gantier, Michael P.; Wang, Yin; Xiang, Dongxi; Wang, Lan; Zhou, Shu Feng; Hou, Yingchun; Wang, Peng; Zhang, Weihong; Pu, Chunwen; Duan, Wei

doi:10.1016/j.canlet.2016.03.045

Cited by 90 publications

(70 citation statements)

References 84 publications

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“…As a type of negatively charged oligonucleotide with molecular weight of approximately 6000 to 10,000 Da, SSOs are generally unable to cross the cell membrane effectively [ 11 ]. Current chemical transfection reagents, whether it is lipid based or polymer-based formulation, the TR/nucleic acid complexes are typically internalized into cells by endocytosis [ 12 ]. After endocytosis, the encapsulated nucleic acid needs to escape from the endosome and release into the cytoplasm to meet their mRNA or miRNA targets or pre-mRNA targets in nucleus.…”

Section: Discussionmentioning

confidence: 99%

Systematic Screening of Commonly Used Commercial Transfection Reagents towards Efficient Transfection of Single-Stranded Oligonucleotides

et al. 2018

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Non-viral vector-mediated transfection is a core technique for in vitro screening of oligonucleotides. Despite the growing interests in the development of oliogonucleotide-based drug molecules in recent years, a comprehensive comparison of the transfection efficacy of commonly used commercial transfection reagents has not been reported. In this study, five commonly used transfection reagents, including Lipofectamine 3000, Lipofectamine 2000, Fugene, RNAiMAX and Lipofectin, were comprehensively analyzed in ten cell lines using a fluorescence imaging-based transfection assay. Although the transfection efficacy and toxicity of transfection reagents varied depending on cell types, the toxicity of transfection reagents generally displayed a positive correlation with their transfection efficacy. According to our results, Lipofectamine 3000, Fugene and RNAiMAX showed high transfection efficacy, however, RNAiMAX may be a better option for majority of cells when lower toxicity is desired. The transfection efficacy of Lipofectamine 2000 was compromised by its high toxicity, which may adversely affect its application in most cells. We firmly believe that our findings may contribute to the future In vitro delivery and screening of single-stranded therapeutic oligonucleotides such as antisense oligonucleotides, antimiRs, and DNAzymes.

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Section: Discussionmentioning

confidence: 99%

Systematic Screening of Commonly Used Commercial Transfection Reagents towards Efficient Transfection of Single-Stranded Oligonucleotides

et al. 2018

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“…Thus, siRNA-based RNA interference (RNAi) offers an invaluable technique for personalized cancer therapy, as it can selectively and effectively knockdown the expression of targeted genes [5,6]. Nevertheless, there are still some obstacles need to be overcome during the development of siRNA-based drugs, including the poor cellular internalization due to the large molecular mass (~13 kDa) and electronegativity of siRNAs, and the instability of siRNAs in blood circulation because of the presence of endonuclease, which greatly hinders the translation of siRNAs from bench to clinical settings [4,7,8].…”

Section: Introductionmentioning

confidence: 99%

Integration of Polylactide into Polyethylenimine Facilitates the Safe and Effective Intracellular siRNA Delivery

et al. 2020

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Polyethylenimine (PEI) is a gold standard polymer with excellent transfection efficacy, yet its severe toxicity and nondegradability hinders its therapeutic application as a gene delivery vector. To tackle this problem, herein we incorporated the biodegradable polylactide (PLA) into the branched PEI by synthesizing a PEI-PLA copolymer via a facile synthetic route. PLA modification significantly improved the cytocompatibility of PEI, PEI-PLA copolymer showed much higher cell viability than PEI as verified in three different human cancer cell lines (HCT116, HepG2 and SKOV3). Interestingly, the PEI-PLA copolymer could effectively bind siRNA targeting PKM2, and the obtained polyplex displayed much higher stability in serum than naked siRNA as determined by agarose gel electrophoresis. Moreover, cellular uptake study demonstrated that PEI-PLA could efficiently deliver the Cy5-labled siRNA into the three tested cancer cell lines, and the transfection efficiency is equivalent to the commercial Lipofectamine® 2000. Finally, it is noteworthy that the polyplex is comparable to Lipo2000 in down-regulating the expression of PKM2 at both mRNA and protein level as measured by q-PCR and western blotting, respectively. Overall, the PEI-PLA copolymer developed in this study has the potential to be developed as a versatile carrier for safe and effective delivery of other nucleic acid-based agents.

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“…However, siRNA-based gene treatment still faces many challenges, such as the poor cellular uptake and low stability in the circulating system. There is much evidence to suggest that the nanocarrier exosomes facilitate siRNA uptake into the targeted cells and improve its pharmacokinetics (Ozcan et al, 2015;Wang et al, 2017). It was reported that the exosome/TRPP2 siRNA complex can efficiently deliver TRPP2 (transient receptor potential polycystic 2) siRNA into FaDu cells and suppress its expression, resulting in the inhibition of the EMT (epithelial-mesenchymal transition) process and reduced invasion of FaDu cells (Wang et al, 2019a).…”

Section: Exosome As Sirna Delivery Systemmentioning

confidence: 99%

The Role of Bone-Derived Exosomes in Regulating Skeletal Metabolism and Extraosseous Diseases

Lyu

Xiao

Guo

et al. 2020

Front. Cell Dev. Biol.

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Bone-derived exosomes are naturally existing nano-sized extracellular vesicles secreted by various cells, such as bone marrow stromal cells, osteoclasts, osteoblasts, and osteocytes, containing multifarious proteins, lipids, and nucleic acids. Accumulating evidence indicates that bone-derived exosomes are involved in the regulation of skeletal metabolism and extraosseous diseases through modulating intercellular communication and the transfer of materials. Following the development of research, we found that exosomes can be considered as a potential candidate as a drug delivery carrier thanks to its ability to transport molecules into targeted cells with high stability, safety, and efficiency. This review aims to discuss the emerging role of bone-derived exosomes in skeletal metabolism and extraosseous diseases as well as their potential role as candidate biomarkers or for developing new therapeutic strategies.

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Challenges and opportunities for siRNA-based cancer treatment

Cited by 90 publications

References 84 publications

Systematic Screening of Commonly Used Commercial Transfection Reagents towards Efficient Transfection of Single-Stranded Oligonucleotides

Systematic Screening of Commonly Used Commercial Transfection Reagents towards Efficient Transfection of Single-Stranded Oligonucleotides

Integration of Polylactide into Polyethylenimine Facilitates the Safe and Effective Intracellular siRNA Delivery

The Role of Bone-Derived Exosomes in Regulating Skeletal Metabolism and Extraosseous Diseases

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