Query: siRNA

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AMF siRNA treatment of keloid through inhibition signaling pathway of RhoA/ROCK1
In conclusion, AMF siRNA is expected to be a novel strategy to treat KD by inhibiting signaling pathway of RhoA/ROCK1.
Source: Genes and Diseases - July 5, 2018 Category: Genetics & Stem Cells Source Type: research

Conserved association of Argonaute 1 and 2 proteins with miRNA and siRNA pathways throughout insect evolution, from cockroaches to flies
Conclusions and general significanceThese basic associations are equivalent to those observed in D. melanogaster, implying that they have been evolutionary conserved from at least cockroach to flies, and possibly stem from the last common ancestor of extant insects.
Source: Biochimica et Biophysica Acta (BBA) Gene Regulatory Mechanisms - July 5, 2018 Category: Genetics & Stem Cells Source Type: research

STAT3-siRNA induced B16.F10 melanoma cell death: more association with VEGF downregulation than p-STAT3 knockdown
Publication date: Available online 30 May 2018Source: Saudi Pharmaceutical JournalAuthor(s): Aws AlshamsanAbstractSTAT3 knockdown by small interfering RNA (siRNA) has been described to inhibit carcinogenic growth in various types of tumors. Earlier we have reported delivery of siRNA by oleic acid- and stearic acid-modified-polyethylenimine and enhancement of silencing of STAT3 by small interfering RNA (siRNA) in B16.F10 melanoma cell lines and consequent tumor suppression. Present investigation mainly focused on the downstream events involved in B16.F10 melanoma cell death and consequent tumor suppression following knockdo...
Source: Saudi Pharmaceutical Journal - July 5, 2018 Category: Drugs & Pharmacology Source Type: research

Characterization of modified mesoporous silica nanoparticles as vectors for siRNA delivery
Publication date: Available online 21 February 2018Source: Asian Journal of Pharmaceutical SciencesAuthor(s): Anna Slita, Anna Egorova, Eudald Casals, Anton Kiselev, Jessica M. RosenholmAbstractGene therapy using siRNA molecules is nowadays considered as a promising approach. For successful therapy, development of a stable and reliable vector for siRNA is crucial. Non-viral and non-organic vectors like mesoporous silica nanoparticles (MSN) are associated with lack of most viral vector drawbacks, such as toxicity, immunogenicity, but also generally a low nucleic acid carrying capacity. To overcome this hurdle, we here modif...
Source: Asian Journal of Pharmaceutical Sciences - July 5, 2018 Category: Drugs & Pharmacology Source Type: research

Enhancing the therapeutic effect via elimination of hepatocellular carcinoma stem cells using Bmi1 siRNA delivered by cationic cisplatin nanocapsules
Publication date: Available online 26 May 2018Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Tan Yang, Yuyuan Chen, Pengxuan Zhao, Huiying Xue, Jia You, Bin Li, Yong Liu, Chuanchuan He, Xiaojuan Zhang, Lingling Fan, Robert J. Lee, Lei Li, Xiang Ma, Chuanrui Xu, Guangya XiangResistance of hepatocellular carcinoma (HCC) to systemic chemotherapy is partially due to presence of drug-resistant cancer stem cells. Bmi1 protein is essential for survival and proliferation of HCC cancer stem cells (CSCs). Here, we report that Bmi1 siRNA (Bmi1siR) loaded in cationic nanocapsules of cisplatin (NPC) eliminated ste...
Source: Nanomedicine: Nanotechnology, Biology and Medicine - July 5, 2018 Category: Nanotechnology Source Type: research

Mannose-conjugated layered double hydroxide nanocomposite for targeted siRNA delivery to enhance cancer therapy
Publication date: Available online 22 June 2017Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Li Li, Run Zhang, Wenyi Gu, Zhi Ping XuAbstractSheet-like layered double hydroxide nanoparticles (LDH NPs) have showed great potentials in biomedical applications such as nanocarriers for drug and gene delivery, biosensors and imaging agents. However, target delivery of drugs and genes using LDH NPs to the desired tumor sites is a major challenge in cancer therapy. The aim of this study is to develop a functional LDH-based nanocomposite for target delivery of siRNA to cancer cells. Mannose as a targeting moie...
Source: Nanomedicine: Nanotechnology, Biology and Medicine - July 5, 2018 Category: Nanotechnology Source Type: research

Lipid-based nanocarriers for siRNA delivery: challenges, strategies and the lessons learned from the DODAX:MO liposomal system.
Abstract The possibility of using the RNA interference (RNAi) mechanisms in gene therapy was one of the scientific breakthroughs of the last century. Despite the extraordinary therapeutic potential of this approach, the need for an efficient gene carrier is hampering the translation of the RNAi technology to the clinical setting. Although a diversity of nanocarriers have been described, liposomes continue to be one of the most attractive siRNA vehicles due to their relatively low toxicity, facilitated siRNA complexation, high transfection efficiency and enhanced pharmacokinetic properties. This review focuses on R...
Source: Current Drug Targets - July 3, 2018 Category: Drugs & Pharmacology Authors: Oliveira ACN, Fernandes J, Goncalves A, Gomes AC, Oliveira R Tags: Curr Drug Targets Source Type: research

Targeted Delivery of siRNA Therapeutics Using Ligand Mediated Biodegradable Polymeric Nanocarriers.
CONCLUSION: In this review, we provide ⅰ) an overview of the non-viral carrier associated with siRNA delivery for cancer treatment, and ⅱ) a description of the five major cancer-targeting ligands. PMID: 29962332 [PubMed - as supplied by publisher]
Source: Current Pharmaceutical Design - July 1, 2018 Category: Drugs & Pharmacology Authors: Jin HS, Soo CK, Hye AM, Sukdeb P, Pill-Hoon C, Sangshetti J, Arote RB Tags: Curr Pharm Des Source Type: research

Molecules, Vol. 23, Pages 1586: The Mechanism for siRNA Transmembrane Assisted by PMAL
nnan Lu The capacity of silencing genes makes small interfering RNA (siRNA) appealing for curing fatal diseases. However, the naked siRNA is vulnerable to and degraded by endogenous enzymes and is too large and too negatively charged to cross cellular membranes. An effective siRNA carrier, PMAL (poly(maleic anhydride-alt-1-decene) substituted with 3-(dimethylamino) propylamine), has been demonstrated to be able to assist siRNA transmembrane by both experiments and molecular simulation. In the present work, the mechanism of siRNA transmembrane assisted by PMAL was studied using steered molecular dynamics simulations bas...
Source: Molecules - June 29, 2018 Category: Chemistry Authors: Yanfei Lu Jipeng Li Nan Su Diannan Lu Tags: Article Source Type: research

Engineered Exosomes for Targeted Transfer of siRNA to HER2 Positive Breast Cancer Cells.
Abstract Exosomes are the best options for gene targeting, because of their natural, nontoxic, non-immunogenic, biodegradable, and targetable properties. By engineering exosome-producing cells, ligands can be expressed fusing with exosomal surface proteins for targeting cancer cell receptors. In the present study, HER2-positive breast cancer cells were targeted with a modified exosome producing engineered HEK293T cell. For this purpose, the HEK293T cells were transduced by a lentiviral vector bearing-LAMP2b-DARPin G3 chimeric gene. Stable cells expressing the fusion protein were selected, and the exosomes produced...
Source: Applied Biochemistry and Biotechnology - June 28, 2018 Category: Biochemistry Authors: Limoni SK, Moghadam MF, Moazzeni SM, Gomari H, Salimi F Tags: Appl Biochem Biotechnol Source Type: research

Cholesterol-grafted chitosan micelles as a nanocarrier system for drug-siRNA co-delivery to the lung cancer cells.
Abstract Combined delivery of a therapeutic small interfering RNA (siRNA) and a chemotherapeutic agent to cancer cells is promising as anticancer therapy, which could offer enhanced cell killing potential and low side effect. However, simultaneous delivery to tumor is challenging. In our study, cholesterol-modified low molecular weight chitosan (MW ~ 15 kDa) was employed as a self-assembled delivery system for both siRNA and a hydrophobic chemotherapeutic agent, curcumin to cancer cells. The siRNA/curcumin loaded nanoparticles (C-CCM/siRNA) were physico-chemically characterized for particle size (165 ± ...
Source: International Journal of Biological Macromolecules - June 25, 2018 Category: Biochemistry Authors: Muddineti OS, Shah A, Rompicharla SVK, Ghosh B, Biswas S Tags: Int J Biol Macromol Source Type: research

Derivation of CYP3A4 and CYP2B6 degradation rate constants in primary human hepatocytes: A siRNA-silencing-based approach.
This study aimed to measure CYP kdeg using siRNA to suppress CYP expression in primary human hepatocytes followed by incubation over a time-course and tracking of protein expression and activity to observe degradation. The magnitude of gene knockdown was determined by qPCR and activity was measured by probe substrate metabolite formation and CYP2B6-Glo™ assay. Protein disappearance was determined by Western blotting. During a time-course of 96 and 60 h of incubation, over 60% and 76% mRNA knockdown was observed for CYP3A4 and CYP2B6, respectively. The kdeg of CYP3A4 and CYP2B6 protein was 0.0138 h-1 (±0.0023) and 0.03...
Source: Drug Metabolism and Pharmacokinetics - June 21, 2018 Category: Drugs & Pharmacology Tags: Drug Metab Pharmacokinet Source Type: research

Acid-degradable Dextran as an Image Guided siRNA Carrier for COX-2 Downregulation
Conclusions: We successfully developed an efficient method to produce an acid-degradable dextran nanopolymer containing cleavable amine groups as the siRNA carrier. Because of its biocompatibility, this degradable dextran delivered COX-2 siRNA within tumors and efficiently downregulated COX-2 expression.
Source: Theranostics - June 20, 2018 Category: Molecular Biology Authors: Zhihang Chen, Balaji Krishnamachary, Marie-France Penet, Zaver M. Bhujwalla Tags: Research Paper Source Type: research

Receptor-targeted aptamer-siRNA conjugate-directed transcriptional regulation of HIV-1
Gene-based therapies represent a promising therapeutic paradigm for the treatment of HIV-1, as they have the potential to maintain sustained viral inhibition with reduced treatment interventions. Such an option may represent a long-term treatment alternative to highly active antiretroviral therapy.Methods: We previously described a therapeutic approach, referred to as transcriptional gene silencing (TGS), whereby small noncoding RNAs directly inhibit the transcriptional activity of HIV-1 by targeting sites within the viral promoter, specifically the 5' long terminal repeat (LTR). TGS differs from traditional RNA interferen...
Source: Theranostics - June 20, 2018 Category: Molecular Biology Authors: Jiehua Zhou, Daniel Lazar, Haitang Li, Xin Xia, Sangeetha Satheesan, Paige Charlins, Denis O'Mealy, Ramesh Akkina, Sheena Saayman, Marc S. Weinberg, John J. Rossi, Kevin V. Morris Tags: Research Paper Source Type: research

Current Transport Systems and Clinical Applications for Small Interfering RNA (siRNA) Drugs
AbstractSmall interfering RNAs (siRNAs) are an attractive new agent with potential as a therapeutic tool because of its ability to inhibit specific genes for many conditions, including viral infections and cancers. However, despite this potential, many challenges remain, including off-target effects, difficulties with delivery, immune responses, and toxicity. Traditional genetic vectors do not guarantee that siRNAs will silence genes in vivo. Rational design strategies, such as chemical modification, viral vectors, and non-viral vectors, including cationic liposomes, polymers, nanocarriers, and bioconjugated siRNAs, provid...
Source: Molecular Diagnosis and Therapy - June 20, 2018 Category: Molecular Biology Source Type: research

siRNA/Lipopolymer Nanoparticles to Arrest Growth of Chronic Myeloid Leukemia Cells In Vitro and In Vivo.
Abstract Therapies for the treatment of Chronic Myeloid Leukemia and other leukemias are still limited for patients at advanced stages, which allow development of point mutations in the BCR-ABL fusion gene that render CML cells insensitive to therapies. An effective non-viral delivery system based on lipopolymers is described in this study to deliver specific siRNAs to CML cells for therapeutic gene silencing. The lipopolymer, based on the lipid α-linolenic acid (αLA) substitution on low molecular weight polyethyleneimine (PEI), was used to deliver siRNA against the BCR-ABL gene and, the resultant therapeutic ef...
Source: European Journal of Pharmaceutics and Biopharmaceutics - June 15, 2018 Category: Drugs & Pharmacology Authors: Valencia-Serna J, Aliabadi HM, Manfrin A, Mohseni M, Jiang X, Uludag H Tags: Eur J Pharm Biopharm Source Type: research

Nanoscale polyelectrolyte complexes encapsulating mRNA and long-chained siRNA for combinatorial cancer gene therapy
Publication date: 25 August 2018 Source:Journal of Industrial and Engineering Chemistry, Volume 64 Author(s): Myung Goo Kim, Sung Duk Jo, Ji Hoon Jeong, Sun Hwa Kim To precisely regulate target genes that are abnormally expressed in cancers, we suggest an RNA-mediated multigene targeting system that co-encapsulates siRNA against vascular endothelial growth factor (VEGF) and mRNA encoding phosphatase and tensin homolog (PTEN). Polymerized long-chain siRNAs (L-siRNAs) formed stable and condensed nanocomplexes with mRNAs using thiolated glycol chitosans (tGCs) as gene carriers. The mRNA/L-siRNA/tGC nanocomplexes (MSNs) exhib...
Source: Journal of Industrial and Engineering Chemistry - June 15, 2018 Category: Chemistry Source Type: research

siRNA Targeting of the SNCG Gene Inhibits the Growth of Gastric Carcinoma SGC7901 Cells in vitro and in vivo by Downregulating the Phosphorylation of AKT/ERK
The aim of the study was to evaluate the effects of synuclein-#x03B3; (SNCG) silencing on gastric cancer SGC7901 cells and to elucidate the associated mechanisms. pGCSIL-lentiviral siRNA targeting of theSNCG gene was employed to inhibitSNCG expression. Several experiments such as quantitative real-time PCR, Western blotting, MTT, colony formation, migration assay, and flow cytometry were performed to investigate the biological behavior of infected SGC7901 cells. BALB/c nude mice were used as tumor xenograft models to assess the effects ofSNCG silencing on tumor growth. Western blot analysis was carried out to determine the...
Source: Cytogenetic and Genome Research - June 14, 2018 Category: Genetics & Stem Cells Source Type: research

The combinational effect of E6/E7 siRNA and anti-miR-182 on apoptosis induction in HPV16-positive cervical cells.
Authors: Javadi H, Lotfi AS, Hosseinkhani S, Mehrani H, Amani J, Soheili ZS, Hojati Z, Kamali M Abstract In the present research, we assumed that reducing the amounts of E6 and E7 oncoproteins by a specific siRNA sequence and recovering p53 and RB proteins, along with the recovery of the FOXO1 protein by applying anti-miR-182, would increase apoptosis and reduce proliferation rate in cancer cells. The HPV16-positive CaSki cervical cancer cell line was used. 48 hours after transfection of siRNA for targeting E6 and E7 oncoproteins and anti-miR-182, expression of its cellular targets p53, p21 and FOXO1 was assessed...
Source: Artificial Cells, Nanomedicine and Biotechnology - June 7, 2018 Category: Biotechnology Tags: Artif Cells Nanomed Biotechnol Source Type: research

siRNA-mediated silencing of CDK8 inhibits proliferation and growth in breast cancer cells Retraction.
Authors: Abstract [This retracts the article on p. 92 in vol. 7, PMID: 24427329.]. PMID: 29874337 [PubMed - in process]
Source: Clinical Breast Cancer - June 7, 2018 Category: Cancer & Oncology Tags: Int J Clin Exp Pathol Source Type: research

STAT3-siRNA induced B16.F10 melanoma cell death: more association with VEGF downregulation than p-STAT3 knockdown
Publication date: Available online 30 May 2018 Source:Saudi Pharmaceutical Journal Author(s): Aws Alshamsan STAT3 knockdown by small interfering RNA (siRNA) has been described to inhibit carcinogenic growth in various types of tumors. Earlier we have reported delivery of siRNA by oleic acid- and stearic acid-modified-polyethylenimine and enhancement of silencing of STAT3 by small interfering RNA (siRNA) in B16.F10 melanoma cell lines and consequent tumor suppression. Present investigation mainly focused on the downstream events involved in B16.F10 melanoma cell death and consequent tumor suppression following knockdown of...
Source: Saudi Pharmaceutical Journal - June 6, 2018 Category: Drugs & Pharmacology Source Type: research

Inhibition of West Nile virus Replication by bifunctional siRNA targeting the NS2A and NS5 Conserved region.
CONCLUSION: Thus this bifunctional siRNA intervention paves the new way for therapeutic treatment of WNV disease. PMID: 29874999 [PubMed - as supplied by publisher]
Source: Current Gene Therapy - June 6, 2018 Category: Genetics & Stem Cells Authors: Karothia D, Dash PK, Parida MM, Bhagyawant S, Kumar JS Tags: Curr Gene Ther Source Type: research

Redox-triggered intracellular siRNA delivery.
Abstract Gene silencing using small interfering RNA (siRNA) is a promising strategy for the treatment of multiple diseases. However, the low in vivo stability of siRNA, its poor pharmacokinetics and inability to penetrate inside cells limit its employment in the clinic. Here, we present a novel redox-sensitive micellar nanopreparation based on a triple conjugate of polyethylene glycol, polyethyleneimine and phosphatidylethanolamine, PEG-SS-PEI-PE (PSSPD). This non-toxic system efficiently condenses siRNA and specifically downregulates target green fluorescent protein (GFP) only under reducing conditions via intrac...
Source: Chemical Communications - June 5, 2018 Category: Chemistry Authors: Mutlu Agardan NB, Sarisozen C, Torchilin VP Tags: Chem Commun (Camb) Source Type: research

Small Delivery Vehicles of siRNA for Enhanced Cancer Targeting.
Abstract Small interfering RNA (siRNA) drugs have been considered to treat various diseases in major organs. However, siRNA drugs developed for cancer therapy are hindered from proceeding to clinics. To date, various delivery formulations have been developed from cationic lipids, polymers, and/or inorganic nanoparticles for systemic siRNA delivery to solid tumors. Most of these delivery vehicles do not generate small particle sizes and pharmacokinetics required for accumulation in target cancer cells, compared with clinically tested anticancer drug-loaded polymeric micelles. This review describes the significance ...
Source: Biomacromolecules - June 4, 2018 Category: Biochemistry Authors: Kim HJ, Yi Y, Kim A, Miyata K Tags: Biomacromolecules Source Type: research

PYGB siRNA inhibits the cell proliferation of human osteosarcoma cell lines.
In conclusion, PYGB siRNA exerted an inhibitory effect on the cell viability of the human osteosarcoma cells MG63 and HOS by blocking the Caspase/Bcl and CDK1 signaling pathway, highlighting novel potential therapeutic methods for treating osteosarcoma. PMID: 29845265 [PubMed - as supplied by publisher]
Source: Molecular Medicine Reports - June 2, 2018 Category: Molecular Biology Tags: Mol Med Rep Source Type: research

STAT3-siRNA induced B16.F10 melanoma cell death: Association with VEGF downregulation than p-STAT3 knockdown
Publication date: Available online 30 May 2018 Source:Saudi Pharmaceutical Journal Author(s): Aws Alshamsan STAT3 knockdown by small interfering RNA (siRNA) has been described to inhibit carcinogenic growth in various types of tumors. Earlier we have reported delivery of siRNA by oleic acid- and stearic acid-modified-polyethylenimine and enhancement of silencing of STAT3 by small interfering RNA (siRNA) in B16.F10 melanoma cell lines and consequent tumor suppression. Present investigation mainly focused on the downstream events involved in B16.F10 melanoma cell death and consequent tumor suppression following knockdown of...
Source: Saudi Pharmaceutical Journal - May 31, 2018 Category: Drugs & Pharmacology Source Type: research

Synthesis of cationic branched tea polysaccharide derivatives for targeted delivery of siRNA to hepatocytes.
Abstract The cationic branched tea polysaccharide (CTPSA) derivative bearing N-acylurea and 3-(dimethylamino)-1-propylamine residues was synthesized and characterized using FTIR and 1H NMR spectroscopy. A nonspecific siRNA (NsiRNA) was used as a model molecule of functional siRNA that could downregulate the over-expressed glycometabolism enzymes in liver. The result of agarose gel electrophoresis confirmed that the CTPSA and NsiRNA could form the stable complexes when their weight ratio was larger than 18. The zeta potentials and sizes the complexes were in the range of +8-+15 mv and 120-150 nm, respectively. ...
Source: International Journal of Biological Macromolecules - May 30, 2018 Category: Biochemistry Authors: Wu S, Li N, Yang C, Yan L, Liang X, Ren M, Yang L Tags: Int J Biol Macromol Source Type: research

Intracellular miRNA or siRNA delivery and function.
Abstract Nanocarrier-mediated delivery and release of short non-coding RNA (e.g., miRNA or siRNA) into the cells with subsequent suppression of the populations of some of the mRNAs and proteins is of interest in the context of the development of a new generation of drugs. Bearing in mind such applications, the author shows the specifics of the corresponding transient kinetics by using three generic models without and with feedback resulting in bistability in the gene expression. In the absence of feedback, the suppression of the mRNA and protein population is transient. In the case of bistable kinetics, non-coding...
Source: Biosystems - May 30, 2018 Category: Biotechnology Authors: Zhdanov VP Tags: Biosystems Source Type: research

Redox-triggered intracellular siRNA delivery
Chem. Commun., 2018, Accepted Manuscript DOI: 10.1039/C8CC01376D, CommunicationNecibe Basaran Mutlu Agardan, Can Sarisozen, Vladimir Torchilin Stimuli-responsive nanopreparations are able to provide drug release in response to various physiological stimuli including redox potential. Gene silencing using small interfering RNA (siRNA) is a promising strategy for the... The content of this RSS Feed (c) The Royal Society of Chemistry
Source: RSC - Chem. Commun. latest articles - May 29, 2018 Category: Chemistry Authors: Necibe Basaran Mutlu Agardan Source Type: research

Galactose Derivative-Modified Nanoparticles for Efficient siRNA Delivery to Hepatocellular Carcinoma.
In this study, we assembled lipid/calcium/phosphate nanoparticles (LCP NPs) conjugated with eight types of galactoside derivatives and demonstrated that phenyl β-d-galactoside-decorated LCP NPs (L4-LCP NPs) exhibited a superior siRNA delivery into HCC cells compared to normal hepatocytes. VEGF siRNAs delivered by L4-LCP NPs downregulated VEGF expression in HCC in vitro and in vivo and led to a potent antiangiogenic effect in the tumor microenvironment of a murine orthotopic HCC model. The efficient delivery of VEGF siRNA by L4-LCP NPs that resulted in significant tumor regression indicates that phenyl galactoside could be...
Source: Biomacromolecules - May 29, 2018 Category: Biochemistry Authors: Huang KW, Lai YT, Chern GJ, Huang SF, Tsai CL, Sung YC, Chiang CC, Hwang PB, Ho TL, Huang RL, Shiue TY, Chen Y, Wang SK Tags: Biomacromolecules Source Type: research

The study of relationships between pKa value and siRNA delivery efficiency based on tri-block copolymers.
Abstract Tri-block copolymers have exhibited great potentials in small interfering RNA (siRNA) therapeutics. To reveal structure-activity relationships, we here synthesized a series of tri-block copolymers with different hydrophobic segments, PEG-PAMA-P(C6Ax-C7Ay-DPAz-DBAm) (EAAS) and PEG-PDAMAEMA-P(C6Ax-C7Ay-DPAz-DBAm) (EDAS), termed from EAASa to EAASh and EDASa to EDASh, with pKa ranging from 5.2 to 7.0. Our data showed that the better gene silencing efficiency was located in pKa of 5.8-6.2, which was contributed from higher endosomal escape observed with confocal images and hemolysis assay. EAASc, the leader p...
Source: Biomaterials - May 29, 2018 Category: Materials Science Authors: Du L, Wang C, Meng L, Cheng Q, Zhou J, Wang X, Zhao D, Zhang J, Deng L, Liang Z, Dong A, Cao H Tags: Biomaterials Source Type: research

Enhancing the therapeutic effect via elimination of hepatocellular carcinoma stem cells using Bmi1 siRNA delivered by cationic cisplatin Nanocapsules
Publication date: Available online 26 May 2018 Source:Nanomedicine: Nanotechnology, Biology and Medicine Author(s): Tan Yang, Yuyuan Chen, Pengxuan Zhao, Huiying Xue, Jia You, Bin Li, Yong Liu, Chuanchuan He, Xiaojuan Zhang, Lingling Fan, Robert J. Lee, Lei Li, Xiang Ma, Chuanrui Xu, Guangya Xiang Resistance of hepatocellular carcinoma (HCC) to systemic chemotherapy is partially due to presence of drug-resistant cancer stem cells. Bmi1 protein is essential for survival and proliferation of HCC cancer stem cells (CSCs). Here, we report that Bmi1 siRNA (Bmi1siR) loaded in cationic nanocapsules of cisplatin (NPC) eliminated ...
Source: Nanomedicine: Nanotechnology, Biology and Medicine - May 27, 2018 Category: Nanotechnology Source Type: research

Poly (amidoamine) (PAMAM) dendrimer mediated delivery of drug and pDNA/siRNA for cancer therapy
Publication date: 30 July 2018 Source:International Journal of Pharmaceutics, Volume 546, Issues 1–2 Author(s): Jun Li, Huamin Liang, Jing Liu, Ziyuan Wang Poly (amidoamine) (PAMAM) dendrimers are well-defined, highly branched macromolecules with numerous active amine groups on the surface. Because of their unique properties, PAMAM dendrimers have steadily grown in popularity in drug delivery, gene therapy, medical imaging and diagnostic application. This review focuses on the recent developments on the application in PAMAM dendrimers as effective carriers for drug and gene (pDNA, siRNA) delivery in cancer therapy, incl...
Source: International Journal of Pharmaceutics - May 26, 2018 Category: Drugs & Pharmacology Source Type: research

Enhancing the therapeutic effect via elimination of hepatocellular carcinoma stem cells using Bmi1 siRNA delivered by cationic cisplatin Nanocapsules
Resistance of hepatocellular carcinoma (HCC) to systemic chemotherapy is partially due to presence of drug-resistant cancer stem cells. Bmi1 protein is essential for survival and proliferation of HCC cancer stem cells (CSCs). Here, we report that Bmi1 siRNA (Bmi1siR) loaded in cationic nanocapsules of cisplatin (NPC) eliminated stem cells in situ HCC in mice. NPC/Bmi1siR was fabricated via electrostatic complexation of Bmi1 siRNA to NPCs, which had cores composed of cisplatin and were coated with cationic lipids.
Source: Nanomedicine : Nanotechnology, Biology, and Medicine - May 26, 2018 Category: Nanotechnology Authors: Tan Yang, Yuyuan Chen, Pengxuan Zhao, Huiying Xue, Jia You, Bin Li, Yong Liu, Chuanchuan He, Xiaojuan Zhang, Lingling Fan, Robert J. Lee, Lei Li, Xiang Ma, Chuanrui Xu, Guangya Xiang Source Type: research

AMF siRNA treatment of keloid through inhibition signaling pathway of RhoA/ROCK1
In conclusion, AMF siRNA is expected to be a novel strategy to treat KD by inhibiting signaling pathway of RhoA/ROCK1.
Source: Genes and Diseases - May 19, 2018 Category: Genetics & Stem Cells Source Type: research

Molecular therapy using siRNA: Recent trends and advances of multi target inhibition of cancer growth.
Abstract RNA interference (RNAi) therapy, harnessed to produce a new class of drugs for treatment, has drawn attention and seen steady progress over the years. Molecular therapy using biological macromolecules small interfering RNA (siRNA) for gene silencing has received significant attention to target cancer-related genes. Basically, siRNA molecules bind to messenger RNAs (mRNA) by complementary base pairing, to induce degradation of the mRNA and/or block protein synthesis. Numerous genes and gene related proteins have been reported till date to target in siRNA based cancer therapy. Furthermore, a combination of ...
Source: International Journal of Biological Macromolecules - May 18, 2018 Category: Biochemistry Authors: Jain S, Pathak K, Vaidya A Tags: Int J Biol Macromol Source Type: research

GSE100403 A kinome-wide high-content siRNA screen identifies MEK5-ERK5 signaling as critical for breast cancer cell EMT and metastasis
Contributors : Simona Pavan ; Nathalie Meyer-Schaller ; Ravi K Kalathur ; Meera Saxena ; Gerhard ChristoforiSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusWe have employed a high-content microscopy screen in combination with a kinome and phosphatome-wide siRNA library to identify signaling pathways underlying an EMT of murine mammary epithelial cells and breast cancer cells. This screen identified the MEK5-ERK5 axis as a critical player in TGFb-mediated EMT. Suppression of MEK5-ERK5 signaling completely prevented the morphological and molecular changes occurring during a TGFb-induced...
Source: GEO: Gene Expression Omnibus - May 17, 2018 Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research

Efficient siRNA transfer to knockdown a placenta specific lncRNA using RGD-modified nano-liposome: A new preeclampsia-like mouse model
Publication date: 30 July 2018 Source:International Journal of Pharmaceutics, Volume 546, Issues 1–2 Author(s): Qianwen Yu, Yue Qiu, Xuhui Wang, Jiajing Tang, Yayuan Liu, Ling Mei, Man Li, Ming Yang, Li Tang, Huile Gao, Zhirong Zhang, Wenming Xu, Qin He Preeclampsia is one of the most serious pregnancy complications. Many animal models have already been developed by researchers to study the pathogenesis and treatment of preeclampsia. However, most of these animal models were established by systemic administration or by surgery in the uterine cavity, which could lead to unwanted systemic toxicity or operative wounds and ...
Source: International Journal of Pharmaceutics - May 17, 2018 Category: Drugs & Pharmacology Source Type: research

Targeted delivery of CD44s-siRNA by ScFv overcomes de novo resistance to cetuximab in triple negative breast cancer
In this study, we show that impaired EGFR degradation is crucial for resistance to cetuximab, which depends on the cell surface molecule CD44. To further investigate the role of CD44 in EGFR signaling and its treatment potential, we developed a targeting fusion protein composed of an anti-EGFR scFv generated from cetuximab and truncated protamine, called Ce-tP. CD44 siRNA can be specifically delivered into EGFR-positive TNBC cells by Ce-tP. Efficient knockdown of CD44 and suppression of both EGFR and downstream signaling by the Ce-tP/siRNA complex were observed in EGFR-positive TNBC cells. More importantly, our results als...
Source: Molecular Immunology - May 17, 2018 Category: Allergy & Immunology Source Type: research

Tuned Density of Anti-Tissue Factor Antibody Fragment onto siRNA-loaded Polyion Complex Micelle for Optimizing Targetability into Pancreatic Cancer Cells.
Abstract Antibody fragment (Fab')-installed polyion complex (PIC) micelles were constructed to improve targetability of small interfering RNA (siRNA) delivery to pancreatic cancer cells. To this end, we synthesized a block copolymer of azide-functionalized poly(ethylene glycol) (PEG) and poly(L-lysine) (PLL), and prepared PIC micelles with siRNA. Then, a dibenzylcyclooctyne (DBCO)-modified anti-human tissue factor (TF) Fab' was conjugated to azido groups on the micellar surface. A fluorescence correlation spectroscopic (FCS) analysis revealed that 1, 2, or 3 molecule(s) of Fab'(s) were installed onto one micellar ...
Source: Biomacromolecules - May 16, 2018 Category: Biochemistry Authors: Min HS, Kim HJ, Ahn J, Naito M, Hayashi K, Toh K, Kim BS, Matsumura Y, Kwon IC, Miyata K, Kataoka K Tags: Biomacromolecules Source Type: research

TRIM24 siRNA induced cell apoptosis and reduced cell viability in human nasopharyngeal carcinoma cells.
Authors: Wang P, Shen N, Liu D, Ning X, Wu D, Huang X Abstract Nasopharyngeal carcinoma (NPC) is a common cancer occurring primarily in East Asia and Africa. The high rate of recurrence and metastasis of NPC continuously endangers the health of patients. The present study aimed to identify the underlying mechanisms involved in the progression of NPC and provide experimental basis to develop a novel and efficient agent against NPC. The present study measured the expression level of tripartite motif containing 24 (TRIM24) in tumor tissues from NPC patients using reverse transcription quantitative polymerase chain re...
Source: Molecular Medicine Reports - May 12, 2018 Category: Molecular Biology Tags: Mol Med Rep Source Type: research

Cellular uptake mechanism and comparative in vitro cytotoxicity studies of monomeric LMWP-siRNA conjugate
Publication date: 25 July 2018 Source:Journal of Industrial and Engineering Chemistry, Volume 63 Author(s): Junxiao Ye, Xing Pei, Hui Cui, Zhili Yu, Hyukjin Lee, Jianxin Wang, Xu Wang, Lu Sun, Huining He, Victor C. Yang The covalent attachment of CPPs to siRNA molecules offers great potential for CPP-mediated siRNA delivery. We recently reported a concise and high-yield synthesis strategy of the cell-permeable, cytosol-dissociable LMWP-siRNA covalent conjugate. Herein, cell uptake mechanism and cellular toxicity studies of this conjugate were performed to evaluate the potential of LMWP-siRNA conjugate for clinical transla...
Source: Journal of Industrial and Engineering Chemistry - May 11, 2018 Category: Chemistry Source Type: research

The siRNA silencing of DcR3 expression induces Fas ligand-mediated apoptosis in HepG2 cells.
Authors: Zhao T, Xu Y, Ren S, Liang C, Zhou X, Wu J Abstract Dysfunctional Fas ligand (FasL) may inhibit the apoptosis of tumor cells. FasL contains two receptors, Fas and Decoy Receptor 3 (DcR3). DcR3 competitively binds to FasL over Fas, resulting in the inhibition of FasL-mediated apoptosis. Therefore, it was suggested that the downregulation of DcR3 expression enhances FasL-mediated apoptosis. In the current study, the expression of DcR3 was silenced in liver cancer HepG2 cells in order to study the effect of FasL on HepG2 cell activity and invasiveness. DcR3 siRNA knockdown HepG2 cells (KD), DcR3 blank plasmid...
Source: Experimental and Therapeutic Medicine - May 9, 2018 Category: General Medicine Tags: Exp Ther Med Source Type: research

Effective gene silencing activity of prodrug-type 2'-O-methyldithiomethyl siRNA compared with non-prodrug-type 2'-O-methyl siRNA.
Abstract Small interfering RNAs (siRNAs) are an active agent to induce gene silencing and they have been studied for becoming a biological and therapeutic tool. Various 2'-O-modified RNAs have been extensively studied to improve the nuclease resistance. However, the 2'-O-modified siRNA activities were often decreased by modification, since the bulky 2'-O-modifications inhibit to form a RNA-induced silencing complex (RISC). We developed novel prodrug-type 2'-O-methyldithiomethyl (MDTM) siRNA, which is converted into natural siRNA in an intracellular reducing environment. Prodrug-type 2'-O-MDTM siRNAs modified at th...
Source: Bioorganic and Medicinal Chemistry Letters - May 8, 2018 Category: Chemistry Authors: Hayashi J, Nishigaki M, Ochi Y, Wada SI, Wada F, Nakagawa O, Obika S, Harada-Shiba M, Urata H Tags: Bioorg Med Chem Lett Source Type: research

Effect of an siRNA Therapeutic Targeting PCSK9 on Atherogenic Lipoproteins: Pre-Specified Secondary End Points in ORION 1.
Conclusions -Inclisiran produces significant and prolonged reductions in atherogenic lipoproteins, suggesting that inhibiting synthesis of PCSK9 through siRNA may be a viable alternative to other approaches which target PCSK9. Clinical Trial Registration -URL: https://www.clinicaltrials.gov. Unique identifier: NCT02597127. PMID: 29735484 [PubMed - as supplied by publisher]
Source: Circulation - May 7, 2018 Category: Cardiology Authors: Ray KK, Stoekenbroek RM, Kallend D, Leiter LA, Landmesser U, Wright RS, Wijngaard P, Kastelein JJ Tags: Circulation Source Type: research

Ultrasound assisted gene and photodynamic synergistic therapy with multifunctional FOXA1-siRNA loaded porphyrin microbubbles for enhancing therapeutic efficacy for breast cancer.
Abstract To improve the non-invasive therapeutic efficacy for ER positive breast cancer (ER+ BC), we fabricated a multifunctional FOXA1 loaded porphyrin microbubble to combine photodynamic therapy (PDT) and gene therapy of FOXA1 knockdown (KD) with ultrasound targeted microbubble destruction (UTMD) technology under the guidance of contrast enhanced ultrasound (CEUS). Cationic porphyrin microbubbles (CpMBs) were firstly fabricated from a porphyrin grafted lipid with two cationic amino groups (PGL-NH2) and fluorocarbon inert gas of C3F8. Porphyrin group in the CpMBs monolayer could be used as a photosensitizer for ...
Source: Biomaterials - May 3, 2018 Category: Materials Science Authors: Zhao R, Liang X, Zhao B, Chen M, Liu R, Sun S, Yue X, Wang S Tags: Biomaterials Source Type: research

Cell-penetrating peptides for siRNA delivery to glioblastomas
In conclusion, we have established an efficient non-covalently complexed carrier (PF14:TG1) for siRNA delivery to human glioblastoma cells (U87), showing a significant two-fold increase in gene-silencing efficiency compared to the parent peptide PF14 and also improved specificity to U87 cells compared to non-glioma targeted cells. Graphical abstract
Source: Peptides - May 1, 2018 Category: Biochemistry Source Type: research

A kinome-wide high-content siRNA screen identifies MEK5–ERK5 signaling as critical for breast cancer cell EMT and metastasis
A kinome-wide high-content siRNA screen identifies MEK5–ERK5 signaling as critical for breast cancer cell EMT and metastasis, Published online: 01 May 2018; doi:10.1038/s41388-018-0270-8A kinome-wide high-content siRNA screen identifies MEK5–ERK5 signaling as critical for breast cancer cell EMT and metastasis
Source: Oncogene - April 30, 2018 Category: Cancer & Oncology Authors: Simona Pavan Nathalie Meyer-Schaller Maren Diepenbruck Ravi Kiran Reddy Kalathur Meera Saxena Gerhard Christofori Source Type: research

Potential of siRNA-albumin complex against cancer.
Abstract RNA interference is a highly specific as well as efficient technology for gene therapy application in molecular oncology. The present study was planned to develop an efficient and stable tumor selective delivery mechanism for siRNA gene therapy for the purpose of both diagnosis as well as therapy. We have used 20 Male wistar rats for the formation of colon cancer model and utilized albumin as carrier molecule for the delivery of siRNA against vascular endothelial growth factor receptor 2 (VEGF R2). The study results confirmed efficient delivery of siRNA at tumor site as confirmed by tagging of siRNA-album...
Source: Chemico-Biological Interactions - April 27, 2018 Category: Molecular Biology Authors: Liu N, Qi YH, Cheng CT, Yang WB, Malhotra A, Zhou Q Tags: Chem Biol Interact Source Type: research

Co-Delivery of Doxorubicin and Anti-BCL-2 siRNA by pH-Responsive Polymeric Vector to Overcome Drug Resistance in In Vitro and In Vivo HepG2 Hepatoma Model.
In this study, triblock copolymer of poly(ethylene glycol)-block-poly(L-lysine)-block-poly aspartyl (N-(N',N'-diisopropylaminoethyl)) (PEG-PLL-PAsp(DIP)) was synthesized for the first time to enable the codelivery of BCL-2 siRNA and DOX. The system is supposed to only bypass drug efflux but also down-regulate the anti-apoptotic gene and consequently confronting against chemoresistance as well. Moreover, the pH responsive ability of the codelivery system can prevent drug leakage during circulation and guarantee swift release at tumors. The codelivered siRNA serves to suppress the expression of anti-apoptotic BCL-2 and conse...
Source: Biomacromolecules - April 24, 2018 Category: Biochemistry Authors: Sun W, Chen X, Xie C, Wang Y, Lin L, Zhu K, Shuai X Tags: Biomacromolecules Source Type: research