Query: siRNA

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Abstract B45: Silencing ss3 integrin by targeted ECO/siRNA nanoparticles inhibits EMT and metastasis of triple-negative breast cancer
Metastatic breast cancer is the second leading cause of cancer-related deaths among women. Triple-negative breast cancer (TNBC) is a highly aggressive subcategory of breast cancer and currently lacks well-defined molecular targets for effective targeted therapies. Disease relapse, metastasis, and drug resistance render standard chemotherapy ineffective in the treatment of TNBC. Because previous studies coupled β3 integrin (ITGB3) to epithelial-mesenchymal transition (EMT) and metastasis, we exploited β3 integrin as a therapeutic target to treat TNBC by delivering β3 integrin siRNA via lipid ECO-based nanoparticles (ECO/...
Source: Cancer Research - January 16, 2017 Category: Cancer & Oncology Authors: Jenny G. Parvani, Maneesh D. Gujrati, Margaret A. Mack, William P. Schiemann, Zheng-Rong Lu Tags: Drug Delivery and Nanomedicine Source Type: research

High-dose BAFF receptor specific mAb-siRNA conjugate generates Fas-expressing B cells in lymph nodes and high-affinity serum autoantibody in a myasthenia mouse model.
Abstract We investigated potential therapeutic effects of a conjugate of BAFF receptor specific- monoclonal antibody and short interference RNA in a mouse model of myasthenia gravis (EAMG). Whereas high-dose siRNA conjugate resulted in significant accumulation of Fas expressing CD19+/ B220+ cells and concurrent expression of type 1 interferon in lymph nodes, low-dose conjugate did not induce FAS expression but caused marked BAFF receptor deficiency in lymph nodes that was further associated with improved MG symptoms. Unexpectedly, despite inhibiting BAFF receptor significantly in PBMCs and secondary lymphoid organ...
Source: Clinical Immunology - January 15, 2017 Category: Allergy & Immunology Authors: Ibtehaj N, Anderson KE, Huda R Tags: Clin Immunol Source Type: research

Therapeutic effects of bach1 siRNA on human breast adenocarcinoma cell line
Conclusion Our results suggest that the bach1 can be considered as a potent adjuvant in breast cancer therapy.
Source: Biomedicine and Pharmacotherapy - January 14, 2017 Category: Drugs & Pharmacology Source Type: research

Therapeutic effects of bach1 siRNA on human breast adenocarcinoma cell line.
CONCLUSION: Our results suggest that the bach1 can be considered as a potent adjuvant in breast cancer therapy. PMID: 28092843 [PubMed - as supplied by publisher]
Source: Biomedicine and pharmacotherapy = Biomedecine and pharmacotherapie - January 13, 2017 Category: Drugs & Pharmacology Authors: Aletaha M, Mansoori B, Mohammadi A, Fazeli M, Baradaran B Tags: Biomed Pharmacother Source Type: research

Targeting NF-kB signaling with polymeric hybrid micelles that co-deliver siRNA and dexamethasone for arthritis therapy.
Abstract The transcription factor NF-kB plays a pivotal role in the pathogenesis of rheumatoid arthritis. Here we attempt to slow arthritis progression by co-delivering the glucocorticoid dexamethasone (Dex) and small-interfering RNA targeting NF-kB p65 using our previously developed polymeric hybrid micelle system. These micelles contain two similar amphiphilic copolymers: polycaprolactone-polyethylenimine (PCL-PEI) and polycaprolactone-polyethyleneglycol (PCL-PEG). The hybrid micelles loaded with Dex and siRNA effectively inhibited NF-kB signaling in murine macrophages more efficiently than micelles containing e...
Source: Biomaterials - January 11, 2017 Category: Materials Science Authors: Wang Q, Jiang H, Li Y, Chen W, Li H, Peng K, Zhang Z, Sun X Tags: Biomaterials Source Type: research

Visualization of self-delivering hydrophobically modified siRNA cellular internalization
siRNAs are a new class of therapeutic modalities with promising clinical efficacy that requires modification or formulation for delivery to the tissue and cell of interest. Conjugation of siRNAs to lipophilic groups supports efficient cellular uptake by a mechanism that is not well characterized. Here we study the mechanism of internalization of asymmetric, chemically stabilized, cholesterol-modified siRNAs (sd-rxRNAs®) that efficiently enter cells and tissues without the need for formulation. We demonstrate that uptake is rapid with significant membrane association within minutes of exposure followed by the formation ...
Source: Nucleic Acids Research - January 9, 2017 Category: Research Authors: Ly, S., Navaroli, D. M., Didiot, M.-C., Cardia, J., Pandarinathan, L., Alterman, J. F., Fogarty, K., Standley, C., Lifshitz, L. M., Bellve, K. D., Prot, M., Echeverria, D., Corvera, S., Khvorova, A. Tags: Chemical Biology and Nucleic Acid Chemistry Source Type: research

Pancreatic Cancer: Targeted Co ‐delivery of PTX and TR3 siRNA by PTP Peptide Modified Dendrimer for the Treatment of Pancreatic Cancer (Small 2/2017)
A new type of tumor‐targeted nanovehicle (PSPGP) is successfully synthesized for co‐delivery of PTX (paclitaxel) and TR3 siRNA, by G. Yu, G. Tang, and co‐workers in article number 1602697. In vitro and in vivo investigations demonstrate that the redox‐responsive PSPGP exhibited enhanced endosomal escape and intracellular degradation, which facilitates PTX and TR3 siRNA release, effectively improving the anti‐tumor efficacy.
Source: Small - January 6, 2017 Category: Nanotechnology Authors: Yang Li, Hebin Wang, Kai Wang, Qinglian Hu, Qi Yao, Youqing Shen, Guocan Yu, Guping Tang Tags: Frontispiece Source Type: research

Molecules, Vol. 22, Pages 86: Novel PEI/Poly-γ-Gutamic Acid Nanoparticles for High Efficient siRNA and Plasmid DNA Co-Delivery
In this study, we created a very high efficient DNA/siRNA co-delivery system by incorporating a negatively-charged poly- γ-glutamic acid (γ-PGA) into PEI/nucleic acid complexes. Spherical nanoparticles with about 200 nm diameter were formed by mixing PEI/plasmid DNA/siRNA/γ-PGA (dual delivery nanoparticles; DDNPs) with specific ratio (N/P/C ratio) and the particles present positive surface charge under all manufact uring conditions. The gel retardation assay shows both nucleic acids were effectively condensed by PEI, even at low N/P ratios. The PEI-based DDNPs reveal excellent DNA/siRNA transfection efficiency in the hu...
Source: Molecules - January 4, 2017 Category: Chemistry Authors: Shu-Fen Peng Hung-Kun Hsu Chun-Cheng Lin Ya-Ming Cheng Kuang-Hsing Hsu Tags: Article Source Type: research

GSE91484 siRNA RNA-seq from K562 (ENCSR100ODO)
Series Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensRNA-seq on K562 cells treated with siRNA targeting NFE2L2.For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf
Source: GEO: Gene Expression Omnibus - January 3, 2017 Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research

GSE91435 siRNA RNA-seq from K562 (ENCSR047MQO)
Series Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensRNA-seq on K562 cells treated with siRNA targeting VEZF1.For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf
Source: GEO: Gene Expression Omnibus - January 3, 2017 Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research

Safety and toxicology of the intravenous administration of Ang2 ‑siRNA plasmid chitosan magnetic nanoparticles.
Safety and toxicology of the intravenous administration of Ang2‑siRNA plasmid chitosan magnetic nanoparticles. Mol Med Rep. 2016 Dec 29;: Authors: Shan X, Xu T, Liu Z, Hu X, Zhang YD, Wang B Abstract This aim of the present study was to investigate the safety and toxicology of intravenous administration of angiopoietin‑2 (Ang2)‑small interfering (si)RNA plasmid‑chitosan magnetic nanoparticles (CMNPs). Ang2‑CMNPs were constructed and subsequently administered at different doses to mice and rats via the tail vein. The acute (in mice) and chronic toxicity (in rats) were observed. The results of ...
Source: Molecular Medicine Reports - January 1, 2017 Category: Molecular Biology Tags: Mol Med Rep Source Type: research

Exosomes from iPSCs Delivering siRNA Attenuate Intracellular Adhesion Molecule-1 Expression and Neutrophils Adhesion in Pulmonary Microvascular Endothelial Cells
In this study, we reprogrammed urine exfoliated renal epithelial cells into human induced pluripotent stem cells (huiPSCs) and purified the exosomes (Exo) from huiPSCs as RNAi delivery system. Through choosing the episomal system to deliver transcription factors, we obtained a non-integrating huiPSCs. Experiments in bothvitro andvivo demonstrated that these huiPSCs possess the pluripotent properties. The exosomes of huiPSCs isolated by differential centrifugation were visualized by transmission electron microscopy (TEM) showing a typical exosomal appearance with an average diameter of 122  nm. Immunoblotting confirmed the...
Source: Inflammation - December 21, 2016 Category: Allergy & Immunology Source Type: research

Injectable, Guest-Host Assembled Polyethylenimine Hydrogel for siRNA Delivery.
Abstract While siRNA has tremendous potential for therapeutic applications, advancement is limited by poor delivery systems. Systemically, siRNAs are rapidly degraded, may have off-target silencing, and necessitate high working concentrations. To overcome this, we developed an injectable, guest-host assembled hydrogel between polyethylenimine (PEI) and polyethylene glycol (PEG) for local siRNA delivery. Guest-host modified polymers assembled with siRNAs to form polyplexes that had improved transfection and viability compared to PEI. At higher concentrations, these polymers assembled into shear-thinning hydrogels t...
Source: Biomacromolecules - December 20, 2016 Category: Biochemistry Authors: Wang LL, Sloand JN, Gaffey AC, Venkataraman CM, Wang Z, Trubelja A, Hammer DA, Atluri P, Burdick JA Tags: Biomacromolecules Source Type: research

Anti-tumor effects of combined doxorubicin and siRNA for pulmonary delivery
In this study, combined doxorubicin (DOX) and Bcl2 siRNA was employed for cancer therapy using polyethylenimine (PEI) as the carrier of Bcl2 siRNA. Most of the DOX and siRNA possessed high cellular uptake efficiency in B16F10 cells, which was proved by FCM and CLSM analysis. Real-time PCR showed that PEI/Bcl2 siRNA exhibited high gene silencing efficiency with 70% Bcl2 mRNA being knocked down. The combination of DOX and siRNA could enhance the cell proliferation inhibition and the cell apoptosis against B16F10 cells compared to free DOX or PEI/Bcl2 siRNA. Furthermore, the biodistribution of DOX and siRNA via pulmonary admi...
Source: Chinese Chemical Letters - December 16, 2016 Category: Chemistry Source Type: research

GSE92309 A specific dsRNA-binding protein complex selectively sequesters endogenous Inverted-Repeat siRNA precursors and inhibits their processing.
Contributors : Thomas Montavon ; Yerim Kwon ; Aude Zimmermann ; Philippe Hammann ; Timoth ée Vincent ; Valérie Cognat ; Fabrice Michel ; Patrice DunoyerSeries Type : Non-coding RNA profiling by high throughput sequencingOrganism : Arabidopsis thalianaIn plants, several dsRNA-binding proteins (DRBs) have been shown to play important roles in various RNA silencing pathways, mostly by promoting the efficiency and/or accuracy of Dicer-like proteins (DCL)-mediated small RNA production. Among the DRBs encoded by the Arabidopsis genome, we recently identified DRB7.2 whose function in RNA silencing was unknown. Here, we show tha...
Source: GEO: Gene Expression Omnibus - December 14, 2016 Category: Genetics & Stem Cells Tags: Non-coding RNA profiling by high throughput sequencing Arabidopsis thaliana Source Type: research

Remodeling of the Extracellular Matrix by Endothelial Cell-Targeting siRNA Improves the EPR-Based Delivery of 100  nm Particles
Remodeling of the Extracellular Matrix by Endothelial Cell-Targeting siRNA Improves the EPR-Based Delivery of 100 nm Particles Molecular Therapy 24, 2090 (December 2016). doi:10.1038/mt.2016.178 Authors: Yu Sakurai, Tomoya Hada, Shoshiro Yamamoto, Akari Kato, Wataru Mizumura & Hideyoshi Harashima
Source: Molecular Therapy - December 14, 2016 Category: Genetics & Stem Cells Authors: Yu Sakurai Tomoya Hada Shoshiro Yamamoto Akari Kato Wataru Mizumura Hideyoshi Harashima Source Type: research

The Niemann-Pick C1 Inhibitor NP3.47 Enhances Gene Silencing Potency of Lipid Nanoparticles Containing siRNA
r R Cullis
Source: Molecular Therapy - December 14, 2016 Category: Genetics & Stem Cells Authors: Haitang Wang Yuen Yi C Tam Sam Chen Josh Zaifman Roy van der Meel Marco A Ciufolini Pieter R Cullis Source Type: research

CARD9 gene silencing with siRNA protects rats against severe acute pancreatitis: CARD9-dependent NF- κB and P38MAPKs pathway.
In this study, small interfering RNA (siRNA) was used to reduce the levels of CARD9 expression in sodium taurocholate-stimulated SAP rats. CARD9 was overexpressed in SAP rats, which correlated with the severity of pancreatitis. When compared to the untreated group, the cohort that received the siRNA treatment demonstrated a significant reduction in pancreatic injury, neutrophil infiltration, myeloperoxidase activity and pro-inflammatory cytokines. Furthermore, siRNAs showed that the reduction of CARD9 in SAP rats down-regulated the expression of NF-κBp65 and P38MAPK which are involved in the transcription and release of a...
Source: J Cell Mol Med - December 13, 2016 Category: Molecular Biology Authors: Yang ZW, Meng XX, Zhang C, Xu P Tags: J Cell Mol Med Source Type: research

Biogenesis of phased siRNAs on membrane-bound polysomes in Arabidopsis
This study reveals global patterns of cytoplasmic partitioning of small RNAs and expands the known functions of ribosomes and ER.DOI:http://dx.doi.org/10.7554/eLife.22750.001
Source: eLife - December 12, 2016 Category: Biomedical Science Tags: A.thaliana argonaute endoplasmic reticulum Genes and Chromosomes microRNA Plant Biology polysome rough ER siRNA Source Type: research

Genome-wide, high-content siRNA screening identifies the Alzheimer ’s genetic risk factor FERMT2 as a major modulator of APP metabolism
AbstractGenome-wide association studies (GWASs) have identified 19 susceptibility loci for Alzheimer ’s disease (AD). However, understanding how these genes are involved in the pathophysiology of AD is one of the main challenges of the “post-GWAS” era. At least 123 genes are located within the 19 susceptibility loci; hence, a conventional approach (studying the genes one by one) would not be time- and cost-effective. We therefore developed a genome-wide, high-content siRNA screening approach and used it to assess the functional impact of gene under-expression on APP metabolism. We found that 832 genes modulated APP m...
Source: Acta Neuropathologica - December 8, 2016 Category: Neurology Source Type: research

Bach1 siRNA attenuates bleomycin-induced pulmonary fibrosis by modulating oxidative stress in mice.
In this study, we knocked down Bach1 using adenovirus-mediated small interfering RNA (siRNA) to determine whether the use of Bach1 siRNA is an effective therapeutic strategy in mice with bleomycin (BLM)‑induced PF. Mouse lung fibroblasts (MLFs) were incubated with transforming growth factor (TGF)-β1 (5 ng/ml) and subsequently infected with recombined adenovirus-like Bach1 siRNA1 and Bach1 siRNA2, while an empty adenovirus vector was used as the negative control. The selected Bach1 siRNA with higher interference efficiency was used for the animal experiments. A mouse model of BLM-induced PF was established, and...
Source: International Journal of Molecular Medicine - December 8, 2016 Category: Molecular Biology Authors: Liu Y, Zheng Y Tags: Int J Mol Med Source Type: research

Exosomes as nanocarriers for siRNA delivery: paradigms and challenges.
Authors: Shahabipour F, Banach M, Sahebkar A Abstract Exosomes are nano-sized vesicles that facilitate intercellular communications through carrying genetic materials and functional biomolecules. Owing to their unique size and structure, exosomes have emerged as a useful tool to overcome the limitations of siRNA delivery. The use of exosomes as siRNA delivery vehicles lacks certain disadvantages of the existing foreign delivery systems such as viruses, polycationic polymers and liposomes, and introduces several advantages including inherent capacity to pass through biological barriers and escape from phagocytosis b...
Source: Archives of Medical Science - December 3, 2016 Category: Journals (General) Tags: Arch Med Sci Source Type: research

Nanoparticles for siRNA-Based Gene Silencing in Tumor Therapy
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 discusses various nanoparticle systems currently used for siRNA delivery for cancer therapy, with emphasis on liposome base...
Source: IEE Transactions on NanoBioscience - December 1, 2016 Category: Nanotechnology Source Type: research

Preliminary study of a novel transfection modality for in vivo siRNA delivery to vocal fold fibroblasts
ConclusionLipitoid effectively knocked down Smad3 expression across multiple transfection conditions. These preliminary data are encouraging, and lipitoid warrants further investigation with the goal of clinical utility. Level of EvidenceNA. Laryngoscope, 2016
Source: The Laryngoscope - December 1, 2016 Category: ENT & OMF Authors: Iv Kraja, Renjie Bing, Nao Hiwatashi, Bernard Rousseau, Danielle Nalband, Kent Kirshenbaum, Ryan C. Branski Tags: Laryngology Source Type: research

CARD9 gene silencing with siRNA protects rats against severe acute pancreatitis: CARD9 ‐dependent NF‐κB and P38MAPKs pathway
In this study, small interfering RNA (siRNA) was used to reduce the levels of CARD9 expression in sodium taurocholate‐stimulated SAP rats. CARD9 was overexpressed in SAP rats, which correlated with the severity of pancreatitis. When compared to the untreated group, the cohort that received the siRNA treatment demonstrated a significant reduction in pancreatic injury, neutrophil infiltration, myeloperoxidase activity and pro‐inflammatory cytokines. Furthermore, siRNAs showed that the reduction of CARD9 in SAP rats down‐regulated the expression of NF‐κBp65 and P38MAPK which are involved in the transcription and rele...
Source: Journal of Cellular and Molecular Medicine - December 1, 2016 Category: Molecular Biology Authors: Zhi ‐wen Yang, Xiao‐xiao Meng, Chun Zhang, Ping Xu Tags: Original Article Source Type: research

Chitosan nanoparticles as a dual drug/siRNA delivery system for treatment of colorectal cancer.
In conclusion, ChNPs encapsulating DOX and snail siRNA can be considered as an effective anti-cancer drugs delivery system for the treatment of colorectal cancer. PMID: 27916629 [PubMed - as supplied by publisher]
Source: Immunology Letters - December 1, 2016 Category: Allergy & Immunology Authors: Sadreddini S, Safaralizadeh R, Baradaran B, Aghebati-Maleki L, Hosseinpour-Feizi MA, Shanehbandi D, Jadidi-Niaragh F, Sadreddini S, Kafil HS, Younesi V, Yousefi M Tags: Immunol Lett Source Type: research

Nanoparticle delivery of siRNA against TWIST to reduce drug resistance and tumor growth in ovarian cancer models
Publication date: Available online 25 November 2016 Source:Nanomedicine: Nanotechnology, Biology and Medicine Author(s): Cai M. Roberts, Sophia Allaf Shahin, Wei Wen, James B. Finlay, Juyao Dong, Ruining Wang, Thanh H. Dellinger, Jeffrey I. Zink, Fuyuhiko Tamanoi, Carlotta A. Glackin Epithelial ovarian cancer (EOC) is the most deadly gynecologic malignancy on account of its late stage at diagnosis and frequency of drug resistant recurrences. Novel therapies to overcome these barriers are urgently needed. TWIST is a developmental transcription factor reactivated in cancers and linked to angiogenesis, metastasis, cancer ste...
Source: Nanomedicine: Nanotechnology, Biology and Medicine - November 25, 2016 Category: Nanotechnology Source Type: research

Development of flexible nanocarriers for siRNA delivery into tumor tissue
Publication date: 10 January 2017 Source:International Journal of Pharmaceutics, Volume 516, Issues 1–2 Author(s): Hyunkyung Jung, Yuri Shimatani, Mahadi Hasan, Kohei Uno, Susumu Hama, Kentaro Kogure Various non-viral delivery systems for small interfering RNAs (siRNA) have been developed. Such delivery systems generally exhibit tightly formed spherical structures. While such carriers have demonstrated good transfection activity in mono-layered cell systems, effects against solid tumors are often less apparent and difficult to demonstrate, likely due to the rigid structures of the carriers, which may prevent penetration...
Source: International Journal of Pharmaceutics - November 25, 2016 Category: Drugs & Pharmacology Source Type: research

Nanoparticle delivery of siRNA against TWIST to reduce drug resistance and tumor growth in ovarian cancer models
Epithelial ovarian cancer (EOC) is the most deadly gynecologic malignancy on account of its late stage at diagnosis and frequency of drug resistant recurrences. Novel therapies to overcome these barriers are urgently needed. TWIST is a developmental transcription factor reactivated in cancers and linked to angiogenesis, metastasis, cancer stem cell phenotype, and drug resistance, making it a promising therapeutic target. In this work, we demonstrate the efficacy of TWIST siRNA (siTWIST) and two nanoparticle delivery platforms to reverse chemoresistance in EOC models.
Source: Nanomedicine : Nanotechnology, Biology, and Medicine - November 24, 2016 Category: Nanotechnology Authors: Cai M. Roberts, Sophia Allaf Shahin, Wei Wen, James B. Finlay, Juyao Dong, Ruining Wang, Thanh H. Dellinger, Jeffrey I. Zink, Fuyuhiko Tamanoi, Carlotta A. Glackin Tags: Original Article Source Type: research

Molecules, Vol. 21, Pages 1594: Multi-Functional Nanogels for Tumor Targeting and Redox-Sensitive Drug and siRNA Delivery
Conclusion: The possibility of releasing biological molecules in a controlled way and to recognize a specific tumor target allows overcoming the typical limits of the classic cancer therapy.
Source: Molecules - November 23, 2016 Category: Chemistry Authors: Giorgia Adamo Natascia Grimaldi Simona Campora Donatella Bulone Maria Bond ì Mohamad Al-Sheikhly Maria Sabatino Clelia Dispenza Giulio Ghersi Tags: Article Source Type: research

Modularized Gold Nanocarriers for TAT ‐Mediated Delivery of siRNA
Targeted delivery of siRNA controlled by near‐infrared light using hollow gold nanoshells has been demonstrated in cancer and stem cells models. Here, a universal surface module and several functionalization rules for the maximized delivery of short nucleic acids (here, siRNA) applicable for diverse gold nanocarriers are described. Streptavidin is devised as a handle to assemble biotinylated cell penetrating peptides (e.g., transactivating transcriptional activator (TAT)), as well as an insulator between the positive charge of TAT and the dense negative charge of RNA. However, direct linking of streptavidin to functional...
Source: Small - November 18, 2016 Category: Nanotechnology Authors: Xiao Huang, Yifan Lai, Gary B. Braun, Norbert O. Reich Tags: Full Paper Source Type: research

Inhibition of hepatitis C virus using siRNA targeted to the virus and Hsp90.
Abstract Hepatitis C (HCV) is a viral disease affecting millions of people worldwide, and persistent HCV infection can lead to progressive liver disease with the development of liver cirrhosis and hepatocellular carcinoma. During treatment for hepatitis C, the occurrence of viral resistance is common. To reduce the occurrence of resistance, new viral treatments should target both viral and cellular factors. Many interactions occur between viral and host proteins during the HCV replication cycle and might be used for the development of new therapies against hepatitis C. Heat shock protein 90 (Hsp90) plays a role in...
Source: Cell Stress and Chaperones - November 17, 2016 Category: Cytology Authors: Braga AC, Carneiro BM, Batista MN, Akinaga MM, Rahal P Tags: Cell Stress Chaperones Source Type: research

CD98 siRNA-loaded nanoparticles decrease hepatic steatosis in mice
Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid hepatic accumulation. Here, we investigated whether a reduction of CD98 expression mediated by CD98 siRNA-loaded nanoparticles (NPs) could attenuate liver disease markers in a mouse model of NAFLD. NPs were generated using a double emulsion/solvent evaporation technique. Mice fed a high fat diet for 8 weeks to induce fatty liver were treated with vein tail injections of CD98 siRNA-loaded NPs. In vitro, HepG2 treated with CD98 siRNA-loaded NPs showed significant downregulation of CD98 leading to a significant decrease of major pro-inflammatory cytokines and markers.
Source: Digestive and Liver Disease - November 17, 2016 Category: Gastroenterology Authors: Brandon S.B. Canup, Heliang Song, Vu Le Ngo, Xiangxiao Meng, Timothy L. Denning, Pallavi Garg, Hamed Laroui Tags: Liver, Pancreas and Biliary Tract Source Type: research

Utility of the 2-Nitrobenzenesulfonamide Group as a Chemical Linker for Enhanced Extracellular Stability and Cytosolic Cleavage in siRNA-Conjugated Polymer Systems.
Abstract Herein we report the 2-nitrobenzenesulfonamide group as a new chemical linker that responds to the difference in redox potential across the cellular membrane, toward the construction of siRNA-polymer conjugates. PEG-conjugated to siRNA via the 2-nitrobenzenesulfonamide group (PEG-sul-siRNA) exhibited highly selective siRNA release under intracellular conditions due to the exclusive presence of GSH/GST ratios in the cell. In addition, siRNA release from PEG-sul-siRNA under extracellular reductive conditions was dramatically suppressed relative to PEG-siRNA conjugates containing a conventional redox-sensiti...
Source: ChemMedChem - November 10, 2016 Category: Chemistry Authors: Huang CH, Takemoto H, Nomoto T, Tomoda K, Matsui M, Nishiyama N Tags: ChemMedChem Source Type: research

Efficient Transfection of siRNA by Peptide Dendrimer-Lipid Conjugates.
Abstract Efficient delivery of small interfering RNA (siRNA) into cells is the basis of target-gene-specific silencing and, ultimately, gene therapy. However, current transfection reagents are relatively inefficient, and very few studies provide the sort of systematic understanding based on structure-activity relationships that would provide rationales for their improvement. This work established peptide dendrimers (administered with cationic lipids) as siRNA transfection reagents and recorded structure-activity relationships that highlighted the importance of positive charge distribution in the two outer layers a...
Source: Chembiochem - November 9, 2016 Category: Biochemistry Authors: Kwok A, Eggimann GA, Heitz M, Reymond JL, Hollfelder F, Darbre T Tags: Chembiochem Source Type: research

STMC-26. MULTIVALENT CATIONIC LIPOSOMES FOR siRNA TRANSFECTION OF PATIENT DERIVED GLIOMA INITIATING CELLS
Glioma initiating cells (GICs) have been implicated as the root cause of treatment failure and tumor recurrence in glioblastoma multiforme (GBM). Therapeutic targeting of GICs is therefore essential to ensure effective treatment without relapse. A novel approach to modulate protein expression in cancer cells is the delivery of siRNAs using liposomes. However, past attempts to transfect cells using neutral liposomes have proven challenging and inefficient owing to the highly refractory nature of these cells. We therefore sought to develop a multivalent cationic liposome (MVCL) formulation for efficient and reproducible...
Source: Neuro-Oncology - November 7, 2016 Category: Cancer & Oncology Authors: Ravi, V., Madhankumar, A. B. Tags: STEM CELLS Source Type: research

Exosome-mediated Delivery of Hydrophobically Modified siRNA for Huntingtin mRNA Silencing
mp; Anastasia Khvorova
Source: Molecular Therapy - November 7, 2016 Category: Genetics & Stem Cells Authors: Marie-C écile Didiot Lauren M Hall Andrew H Coles Reka A Haraszti Bruno MDC Godinho Kathryn Chase Ellen Sapp Socheata Ly Julia F Alterman Matthew R Hassler Dimas Echeverria Lakshmi Raj David V Morrissey Marian DiFiglia Neil Aronin Anastasia Khvorova Source Type: research

Cell Type-Specific Responses of Peripheral Blood CD14-Positive Monocytes to Liposome-Encapsulated Immunostimulatory siRNA.
Abstract RNA interference via small interfering RNA (siRNA) has many potential therapeutic applications, and liposomal-based systems are useful for improving the pharmacokinetics of siRNAs, including their intracellular release and distribution. However, for the successful translation of this technology into clinical applications, it is important to understand how liposomal encapsulation changes the cellular uptake and immunostimulatory adverse effects of siRNAs. Here we evaluated the cellular uptake and innate immune activation by an immunostimulatory siRNA encapsulated within a liposome carrier in commercially a...
Source: Biological and Pharmaceutical Bulletin - November 4, 2016 Category: Drugs & Pharmacology Authors: Abe Y, Sakai-Kato K, Goda Y Tags: Biol Pharm Bull Source Type: research

Enhanced Anti-Tumor Efficacy of Lipid-Modified Platinum Derivatives in Combination with Survivin Silencing siRNA in Resistant Non-Small Cell Lung Cancer
ConclusionsCo-treatment of lipid-modified compounds andsurvivin-silencing siRNA can constitute a reliable alternative to cisplatin treatment for cisplatin-resistant lung tumors that merit further evaluation.
Source: Pharmaceutical Research - November 3, 2016 Category: Drugs & Pharmacology Source Type: research

Endocytic Transport of Polyplex and Lipoplex siRNA Vectors in HeLa Cells
ConclusionsMP, CvME and FME, but not the acidified clathrin-mediated pathway, lead to effective gene silencing by PEI/siRNA polyplexes. Lipoplexes, in contrast, deliver siRNA primarily by direct fusion of the liposomal and cellular membranes. These results provide a new understanding of the mechanisms of siRNA delivery materials in HeLa cells and may aid in design of more effective RNAi strategies.
Source: Pharmaceutical Research - November 3, 2016 Category: Drugs & Pharmacology Source Type: research

Lipophilic 2'-O-Acetal Ester RNAs: Synthesis, Thermal Duplex Stability, Nuclease Resistance, Cellular Uptake, and siRNA Activity after Spontaneous Naked Delivery.
We report the synthesis and the biochemical and biophysical characteristics of 2'-O-phenylisobutyryloxymethyl (PiBuOM)-modified siRNAs and their impact on biological activity. In the case of spontaneous cellular uptake of naked PiBuOM-modified siRNA, we observed increased target suppression in human cells relative to unmodified or pivaloyloxymethyl (PivOM)-modified siRNA. We provide evidence of improved spontaneous cellular uptake of naked PiBuOM-modified siRNA and of substantial target suppression in human cells in serum-containing medium. PMID: 27569765 [PubMed - in process]
Source: Chembiochem - November 3, 2016 Category: Biochemistry Authors: Biscans A, Bertrand JR, Dubois J, Rüger J, Vasseur JJ, Sczakiel G, Dupouy C, Debart F Tags: Chembiochem Source Type: research

Multifunctional superparamagnetic nanoparticles: from synthesis to siRNA delivery.
Abstract Targeted delivery of small interfering RNA (siRNA) to specific tumor tissues and cells remains as one of the key challenges in the development of RNA interference as a therapeutic application. To target breast cancer, we developed a cationic nanoparticle as a therapeutic delivery system. The successful synthesis of the magnetic nanoparticles modified by polyaspartate (PAA) and polyethyleneimine (PEI) was confirmed using fourier transform infrared (FT-IR) measurements. The designed nanoparticle has been characterized evaluating its size and charge before and after nanoplex formation with siRNA. The designe...
Source: Current Pharmaceutical Design - October 31, 2016 Category: Drugs & Pharmacology Authors: Arami S, Mahdavi M, Rashidi MR, Fathi M, Hejazi MS, Samadi N Tags: Curr Pharm Des Source Type: research

Multiple siRNA delivery against cell cycle and anti-apoptosis proteins using lipid-substituted polyethylenimine in triple-negative breast cancer and nonmalignant cells.
Abstract Conventional breast cancer therapies have significant limitations that warrant a search for alternative therapies. Short-interfering RNA (siRNA), delivered by polymeric biomaterials and capable of silencing specific genes critical for growth of cancer cells, holds great promise as an effective, and more specific therapy. Here, we employed amphiphilic polymers and silenced the expression of two cell cycle proteins, TTK and CDC20, and the anti-apoptosis protein survivin to determine the efficacy of polymer-mediated siRNA treatment in breast cancer cells as well as side effects in nonmalignant cells in vitro...
Source: Biomed Res - October 29, 2016 Category: Research Authors: Parmar MB, Arteaga Ballesteros BE, Fu T, K C RB, Montazeri Aliabadi H, Hugh JC, Löbenberg R, Uludağ H Tags: J Biomed Mater Res A Source Type: research

Non-viral xylosyltransferase-1 siRNA delivery as an effective alternative to chondroitinase in an in vitro model of reactive astrocytes
In this study we investigate the ability of small interfering RNA (siRNA) delivered by a non-viral polymer vector to silence the rate-limiting enzyme involved in CSPG synthesis. Gene expression of this enzyme, xylosyltransferase-1, was silenced by 65% in Neu7 astrocytes which conferred a reduced expression of CSPGs. Furthermore, conditioned medium taken from treated Neu7s, or co-culture experiments with dorsal root ganglia (DRG) showed that siRNA treatment resulted in a more permissive environment for DRG neurite outgrowth than treatment with chondroitinase ABC alone. These results indicate that there is a role for targete...
Source: Neuroscience - October 27, 2016 Category: Neuroscience Source Type: research

CXCR4-targeted modular peptide carriers for efficient anti-VEGF siRNA delivery
Publication date: 30 December 2016 Source:International Journal of Pharmaceutics, Volume 515, Issues 1–2 Author(s): Anna Egorova, Anastasia Shubina, Dmitriy Sokolov, Sergey Selkov, Vladislav Baranov, Anton Kiselev The application of small interfering RNA (siRNA) for specific gene inhibition is a promising strategy in gene therapy treatments. The efficient cellular delivery of therapeutic siRNA is a critical step in RNA interference (RNAi) application. Highly efficient siRNA carriers should be developed for specific cellular uptake, stable RNA-complexes formation and intracellular RNA release. To study these features, we...
Source: International Journal of Pharmaceutics - October 27, 2016 Category: Drugs & Pharmacology Source Type: research

Preparation and In Vitro Evaluation of Vaginal Formulations Including siRNA and Paclitaxel-Loaded SLNs for Cervical Cancer.
This study indicate that vaginal suppository containing SLNs can bring the advantages of the simultaneous delivery of paclitaxel and siRNA via vaginal route with no help from professionals. PMID: 27793757 [PubMed - as supplied by publisher]
Source: European Journal of Pharmaceutics and Biopharmaceutics - October 25, 2016 Category: Drugs & Pharmacology Authors: Büyükköroğlu G, Şenel B, Başaran E, Yenilmez E, Yazan Y Tags: Eur J Pharm Biopharm Source Type: research

SiRNA/DOX lodeded chitosan based nanoparticles: Development, Characterization and in vitro evaluation on A549 lung cancer cell line.
Authors: Seifi-Najmi M, Hajivalili M, Safaralizadeh R, Sadreddini S, Esmaeili S, Razavi R, Ahmadi M, Mikaeili H, Baradaran B, Shams-Asenjan K, Yousefi M Abstract High-mobility group AT-hook2 (HMGA2), involved in epithelial mesenchymal transition (EMT) process, has a pivotal role in lung cancer metastasis. Lung cancer therapy with HMGA2 suppressing small interfering RNA (siRNA) has been introduced recently while doxorubicin (DOX) has been used as a frequent cancer chemotherapy agent. Both reagents have been faced with obstacles in clinic which make them ineffective. NanoParticles (NPs) provided a platform for effici...
Source: Cellular and Molecular Biology - October 20, 2016 Category: Molecular Biology Tags: Cell Mol Biol (Noisy-le-grand) Source Type: research

Tackling breast cancer chemoresistance with nano-formulated siRNA
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Source: Gene Therapy - October 20, 2016 Category: Genetics & Stem Cells Authors: S K Jones O M Merkel Source Type: research

Targeted Co ‐delivery of PTX and TR3 siRNA by PTP Peptide Modified Dendrimer for the Treatment of Pancreatic Cancer
A new type of tumor‐targeted nanovehicle peptide‐conjugated PSPG (PSPGP) is successfully synthesized for co‐delivery of paclitaxel (PTX) and TR3 small interfering RNA (siRNA). In vitro and in vivo investigations demonstrate that the redox‐responsive PSPGP exhibit enhanced endosomal escape and intracellular degradation, which facilitate PTX and TR3 siRNA release, effectively improving the antitumor efficacy.
Source: Small - October 20, 2016 Category: Nanotechnology Authors: Yang Li, Hebin Wang, Kai Wang, Qinglian Hu, Qi Yao, Youqing Shen, Guocan Yu, Guping Tang Tags: Communication Source Type: research

Molecules, Vol. 21, Pages 1314: Synthesis of Polymer-Lipid Nanoparticles by Microfluidic Focusing for siRNA Delivery
Polyethylenimine (PEI) as a cationic polymer is commonly used as a carrier for gene delivery. PEI-800 is less toxic than PEI-25K but it is also less efficient. A novel nanocarrier was developed by combining PEI-800 with a pH-sensitive lipid to form polymer-lipid hybrid nanoparticles (P/LNPs). They were synthesized by microfluidic focusing (MF). Two microfluidic devices were used to synthesize P/LNPs loaded with VEGF siRNA. A series of P/LNPs with different particle sizes and distributions were obtained by altering the flow rate and geometry of microfluidic chips, and introducing sonication. Furthermore, the P/LNPs can be l...
Source: Molecules - October 17, 2016 Category: Chemistry Authors: Yujing Li Xueqin Huang Robert Lee Yuhang Qi Kaikai Wang Fei Hao Yu Zhang Jiahui Lu Qingfan Meng Shuai Li Jing Xie Lesheng Teng Tags: Article Source Type: research