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Total 14361 results found since Jan 2013.
RNAi-mediated knockdown of mouse melanocortin-4 receptor in vitro and in vivo, using an siRNA expression construct based on the mir-187 precursor.
Authors: Kato M, Huang YY, Matsuo M, Takashina Y, Sasaki K, Horai Y, Juni A, Kamijo SI, Saigo K, Ui-Tei K, Tei H Abstract RNA interference (RNAi) is a powerful tool for the study of gene function in mammalian systems, including transgenic mice. Here, we report a gene knockdown system based on the human mir-187 precursor. We introduced small interfering RNA (siRNA) sequences against the mouse melanocortin-4 receptor (mMc4r) to alter the targeting of miR-187. The siRNA-expressing cassette was placed under the control of the cytomegalovirus (CMV) early enhancer/chicken β-actin promoter. In vitro, the construct effici...
Source: Experimental Animals - October 14, 2016 Category: Research Tags: Exp Anim Source Type: research
Quantum dot ‐mediated delivery of siRNA to inhibit sphingomyelinase activities in brain‐derived cells
Abstract The use of RNAi to suppress protein synthesis offers a potential way of reducing the level of enzymes or the synthesis of mutant toxic proteins but there are few tools currently available for their delivery. To address this problem, bioconjugated quantum dots (QDs) containing a hydrophobic component (N‐palmitate) and a sequence VKIKK designed to traverse across cell membranes and visualize drug delivery were developed and tested on cell lines of brain origin. We used the Zn outer shell of the QD to bind HIS6 in JB577 (W•G•Dap(N‐Palmitoyl)•VKIKK•P9•G2•H6) and by a gel‐shift assay showed that siRNA...
Source: Journal of Neurochemistry - October 13, 2016 Category: Neuroscience Authors: Ted Getz, Jingdong Qin, Igor L. Medintz, James B. Delehanty, Kimihiro Susumu, Philip E. Dawson, Glyn Dawson Tags: Original Article Source Type: research
Guide Strand 3'-End Modifications Regulate siRNA Specificity.
Abstract Short interfering RNA (siRNA)-triggered gene knockdown via the RNA interference (RNAi) pathway is widely used to study gene function and siRNA-based therapeutics are in development.However, since the guide strand of an siRNA can function like a natural microRNA (miRNA), siRNAs often repress hundreds of off-target transcripts with complementary only to the seed region (nucleotides 2-8) of the guide strand. Here we describe novel guide strand 3' end modifications derived from 1-ethynylribose and copper-catalyzed azide/alkyne cycloaddition reactions and evaluate their impact on target vs miRNA-like off-targe...
Source: Chembiochem - October 11, 2016 Category: Biochemistry Authors: Valenzuela RA, Onizuka K, Ball-Jones A, Hu T, Suter SR, Beal PA Tags: Chembiochem Source Type: research
Knockdown of Long Noncoding RNA uc.338 by siRNA Inhibits Cellular Migration and Invasion in Human Lung Cancer Cells.
Authors: Gao X, Gao X, Li C, Zhang Y, Gao L Abstract Lung cancer remains a critical health concern worldwide. Long noncoding RNAs with ultraconserved elements have recently been implicated in human tumorigenesis. The present study investigated the role of ultraconserved element 338 (uc.338) in the regulation of cell proliferation and metastasis in human lung cancer. Our data showed that the expression of uc.338 in lung cancer was remarkably increased in vivo and in vitro. Depletion of uc.338 with specific siRNA interference retarded the cell proliferative rate in lung cancer cell lines NCI-H929 and H1688. Furthermo...
Source: Oncology Research - October 11, 2016 Category: Cancer & Oncology Tags: Oncol Res Source Type: research
Mechanisms of cellular uptake and endosomal escape of calcium-siRNA nanocomplexes
Publication date: 30 December 2016 Source:International Journal of Pharmaceutics, Volume 515, Issues 1–2 Author(s): Matan Goldshtein, Efrat Forti, Emil Ruvinov, Smadar Cohen Ca2+-siRNA nanocomplexes represent a simple yet an effective platform for siRNA delivery into the cell cytoplasm, with subsequent successful siRNA-induced target gene silencing. Herein, we aimed to elucidate the roles played by calcium ions in siRNA nanocomplex formation, cell uptake, and endosomal escape. We investigated whether the replacement of Ca2+in the nanocomplex by other bivalent cations would affect their cell entry and subsequent gene sil...
Source: International Journal of Pharmaceutics - October 9, 2016 Category: Drugs & Pharmacology Source Type: research
Molecules, Vol. 21, Pages 1334: Targeted Delivery of siRNA to Transferrin Receptor Overexpressing Tumor Cells via Peptide Modified Polyethylenimine
In conclusion, the HAI peptide may be useful to target TfR overexpressing tumors in targeted gene and siRNA delivery approaches.
Source: Molecules - October 9, 2016 Category: Chemistry Authors: Yuran Xie Bryan Killinger Anna Moszczynska Olivia Merkel Tags: Article Source Type: research
Single-Step Microfluidic Synthesis of Transferrin-Conjugated Lipid Nanoparticles for siRNA Delivery
In this study, a single-step process based on microfluidic focusing (MF) was employed to synthesize transferrin-conjugated lipid nanoparticles (Tf-LNPs) and the method was compared with a multi-steps bulk mixing (BM) method. The results indicate that this single-step MF process enables rapid and efficient synthesis of Tf-LNPs, which were named Tf-LNPs-MF. Tf-LNPs-MF was shown to have a smaller size and more uniform structures compared to LNPs produced by multi-steps BM method (Tf-LNPs-BM). Furthermore, efficient cellular uptake of Tf-LNPs-MF in vitro as well as greater tumor inhibition in vivo proved that Tf-LNPs-MF had hi...
Source: Nanomedicine: Nanotechnology, Biology and Medicine - October 9, 2016 Category: Nanotechnology Source Type: research
siRNA-coupled nanoparticles for improved therapeutic targeting of pancreatic cancer
Pancreatic cancer (PC) is one of the most lethal malignancies, characterised by a poor response to conventional chemotherapy and rapid development of secondary resistances. Compared with most other digestive tract cancers, progress in PC treatment has been miniscule over the past decades. The most frequently mutated genes, KRAS and p53, are still difficult to target, and so far only EGFR inhibition (erlotinib) is routinely used in clinical practice for targeted therapy. PC treatment is further complicated by a dense tumour stroma and low vessel density, leading to impaired drug delivery and high adverse effects of systemic...
Source: Gut - October 6, 2016 Category: Gastroenterology Authors: Lange, S., Saur, D., Rad, R. Tags: Commentary Source Type: research
Tumour-specific delivery of siRNA-coupled superparamagnetic iron oxide nanoparticles, targeted against PLK1, stops progression of pancreatic cancer
Conclusions Our data suggest siPLK1-StAv-SPIONs with dual specificity residues for tumour targeting and membrane translocation to represent an exciting opportunity for targeted therapy in patients with PDAC.
Source: Gut - October 6, 2016 Category: Gastroenterology Authors: Mahajan, U. M., Teller, S., Sendler, M., Palankar, R., van den Brandt, C., Schwaiger, T., Kühn, J.-P., Ribback, S., Glöckl, G., Evert, M., Weitschies, W., Hosten, N., Dombrowski, F., Delcea, M., Weiss, F.-U., Lerch, M. M., Mayerle, J. Tags: Pancreas and biliary tract, Open access, Pancreatic cancer Source Type: research
Comparing gene silencing and physiochemical properties in siRNA bound cationic star-polymer complexes.
Abstract The translation of siRNA into clinical therapies has been significantly delayed by issues surrounding the delivery of naked siRNA to target cells. Here we investigate siRNA delivery by cationic acrylic polymers developed by Reversible Addition Fragmentation chain Transfer (RAFT) mediated free radical polymerization. We investigated cell uptake and gene silencing of a series of siRNA-star polymer complexes both in the presence and absence of a protein "corona". Using a multidisciplinary approach including quantitative nanoscale mechanical-atomic force microscopy, dynamic light scattering and nanoparticle t...
Source: Biomacromolecules - October 5, 2016 Category: Biochemistry Authors: Dearnley M, Reynolds NP, Cass P, Wei X, Shi S, Mohammed AA, Le T, Gunatillake P, Tizard ML, Thang SH, Hinton TM Tags: Biomacromolecules Source Type: research
Novel polyacrylate-based cationic nanoparticles for survivin siRNA delivery combined with mitoxantrone for treatment of breast cancer
Publication date: Available online 3 October 2016 Source:Biologicals Author(s): Sanam Arami, Majid Mahdavi, Mohammad Reza Rashidi, Marziyeh Fathi, Mohammad-saeid Hejazi, Nasser Samadi As a gene delivery method in breast cancer therapy, knocking down the undesired genes in the cancerous cells would be promising. Inhibitors of Apoptosis Protein (IAP) family genes are some of the genes whose responsibility is inhibition of apoptosis in cells. Silencing these genes seems to be helpful directing the tumor cells to death. siRNA sequence designed against survivin anti-apoptotic gene can play this role if carried to the cytoplasm...
Source: Biologicals - October 3, 2016 Category: Biology Source Type: research
Neurobasal media facilitates increased specificity of siRNA-mediated knockdown in primary cerebellar cultures
Conclusions Specific knockdown of target can be achieved in primary cerebellar granule cells using Accell siRNAs in Neurobasal™ media. This method ensures specific knockdown in post-mitotic neurons without the need for biosafety level 2 laboratories, additional reagents, or instruments needed by other transfection
Source: Journal of Neuroscience Methods - October 3, 2016 Category: Neuroscience Source Type: research
Novel polyacrylate-based cationic nanoparticles for survivin siRNA delivery combined with mitoxantrone for treatment of breast cancer.
Abstract As a gene delivery method in breast cancer therapy, knocking down the undesired genes in the cancerous cells would be promising. Inhibitors of Apoptosis Protein (IAP) family genes are some of the genes whose responsibility is inhibition of apoptosis in cells. Silencing these genes seems to be helpful directing the tumor cells to death. siRNA sequence designed against survivin anti-apoptotic gene can play this role if carried to the cytoplasm. Here we prepared a positive charged biocompatible nano-sized particle made up of a Fe3O4 core covered respectively by polyacrylate (PA) and polyethyleneimine (PEI) l...
Source: Biologicals : Journal of the International Association of Biological Standardization - October 2, 2016 Category: Biotechnology Authors: Arami S, Mahdavi M, Rashidi MR, Fathi M, Hejazi MS, Samadi N Tags: Biologicals Source Type: research
Conjugates of HA2 with octaarginine-grafted HPMA copolymer offer effective siRNA delivery and gene silencing in cancer cells.
Abstract The key for successful gene silencing is to design a safe and efficient siRNA delivery system for the transfer of therapeutic nucleic acids into the target cells. Here, we describe the design of hydrophilic N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer displaying multiple copies of octaarginine (R8) and its use in promoting the effective delivery of small interfering RNA (siRNA) molecules intracellularly. Fluorescein-5-isothiocyanate (FITC)-labeled HPMA copolymer-bound R8 (P-R8-FITC) was synthesized with increasing R8 molar ratios (4 to 9.5 mol-%) to define the optimal R8 content that allowed the pol...
Source: European Journal of Pharmaceutics and Biopharmaceutics - September 30, 2016 Category: Drugs & Pharmacology Authors: Golan M, Feinshtein V, David A Tags: Eur J Pharm Biopharm Source Type: research
GSE87497 Evaluating Side Effects of Nanoparticle-mediated siRNA Delivery to Mesenchymal Stem Cells Using Next-generation Sequencing and Enrichment Analysis
This study investigates both intended and unintended effects of diblock copolymer nanoparticle (NP) delivery of siRNA delivery to human mesenchymal stem cells (hMSC). Specifically, siRNA delivery was investigated at a range of NP-siRNA:hMSC ratios with a focus on the effects of NP-siRNA treatment on hMSC functions. Additionally, next-generation RNA sequencing (RNA-seq) was used with enrichment analysis to observe side effects in hMSC gene expression. Results show NP-siRNA delivery is negatively correlated with hMSC density. However, higher NP-siRNA:hMSC ratios increased cytotoxicity and decreased metabolic activity. hMSC p...
Source: GEO: Gene Expression Omnibus - September 30, 2016 Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
Molecules, Vol. 21, Pages 1279: Development of an Innovative Intradermal siRNA Delivery System Using a Combination of a Functional Stearylated Cytoplasm-Responsive Peptide and a Tight Junction-Opening Peptide
In this study, we examined intradermal siRNA permeability in the tape-stripped (20 times) back skin of mice or AD-like skin of auricles treated with 6-carboxyfluorescein-aminohexyl phosphoramidite (F AM)-labeled siRNA, the tight junction modulator AT1002, and the functional cytoplasm-responsive stearylated peptide STR-CH2R4H2C by using confocal laser microscopy. We found that strong fluorescence was observed deep and wide in the epidermis and dermis of back skin and AD-like ears after siRNA with STR-CH2R4H2C and AT1002 treatment. After 10 h from administration, brightness of FAM-siRNA was significantly higher for STR-CH2R4...
Source: Molecules - September 23, 2016 Category: Chemistry Authors: Hisako Ibaraki Takanori Kanazawa Yuuki Takashima Hiroaki Okada Yasuo Seta Tags: Article Source Type: research
P10.06 Oxamate attenuates aerobic glycolysis, motility, viability and proliferation of medulloblastoma but LDHA siRNA does not
Conclusions:It is possible that oxamate inhibits multiple LDH family members as the active site for LDH isoenzymes, comprised of LDHA and LDHB subunits are identical. The results of further investigations will be critical as LDHA may prove to be an inadequate target for MB and a broader LDH family inhibitor or lactate inhibitor may be more appropriate. However these studies, combined with extensive research into the literature, support the concept and provide proof of principle that targeting aerobic glycolysis and lactate production in medulloblastoma is worthwhile therapeutic avenue worth pursuing further.
Source: Neuro-Oncology - September 20, 2016 Category: Cancer & Oncology Authors: Valvona, C. J., Pilkington, G. J. Tags: P10 Pediatric brain tumours Source Type: research
BACH1 silencing by siRNA inhibits migration of HT-29 colon cancer cells through reduction of metastasis-related genes
Conclusion Our results indicated that BACH1 down-regulation in HT29 CRC cells had no effect on cell growth but did inhibit cell migration by decreasing metastasis-related genes expression. Collectively, these results suggest that BACH1 may function as an oncogenic driver in colon cancer and may represent as a potential target of gene therapy for CRC treatment.
Source: Biomedicine and Pharmacotherapy - September 19, 2016 Category: Drugs & Pharmacology Source Type: research
BACH1 silencing by siRNA inhibits migration of HT-29 colon cancer cells through reduction of metastasis-related genes.
CONCLUSION: Our results indicated that BACH1 down-regulation in HT29 CRC cells had no effect on cell growth but did inhibit cell migration by decreasing metastasis-related genes expression. Collectively, these results suggest that BACH1 may function as an oncogenic driver in colon cancer and may represent as a potential target of gene therapy for CRC treatment. PMID: 27657827 [PubMed - as supplied by publisher]
Source: Biomedicine and pharmacotherapy = Biomedecine and pharmacotherapie - September 18, 2016 Category: Drugs & Pharmacology Authors: Davudian S, Shajari N, Kazemi T, Mansoori B, Salehi S, Mohammadi A, Shanehbandi D, Shahgoli VK, Asadi M, Baradaran B Tags: Biomed Pharmacother Source Type: research
GSE86924 Effect of NR4A3 siRNA treatment on gene expression of islet derived hybrid cell of 1.1B4
Contributors : Yuzuru Otsuka ; Motoko Yamada ; Etsuko UetaSeries Type : Expression profiling by arrayOrganism : Homo sapiensGene regulation associated with antioxidant defense system in pancreatic beta cells still needs to be elucidated, we found NR4A3 gene expression was up-regulated with 100mM H2O2, therefore, we analyzed the genes expression with Agilent micro-array after NR4A3 siRNA4 treatment by one color method, and found 1044 genes were up-regulated and 859 genes were down regulated in NR4A3 knocked down cell. Changes of some genes expressions were confirmed by real time PCR.The genes of 1044 in NR4A3 siRNA treated ...
Source: GEO: Gene Expression Omnibus - September 15, 2016 Category: Genetics & Stem Cells Tags: Expression profiling by array Homo sapiens Source Type: research
siRNA-Mediated Silencing of HMGA2 Induces Apoptosis and Cell Cycle Arrest in Human Colorectal Carcinoma
ConclusionsThese results propose that HMGA2 might play an important role in the progression of colorectal carcinoma and might be a potential therapeutic target for trigger apoptosis and cell cycle arrest in colorectal carcinoma.
Source: Journal of Gastrointestinal Cancer - September 13, 2016 Category: Cancer & Oncology Source Type: research
Effect of Smo SiRNA-mediated Hedgehog Signaling Pathway Inhibition on Palatal Fusion
Publication date: August 2016 Source:Biomedical and Environmental Sciences, Volume 29, Issue 8 Author(s): Qian ZHOU, WU Feng Hai, Yuan WEI, Li ZHU Wen We used Smo siRNA to inhibit hedgehog signaling pathway in embryonic day (E) 13 palatal shelves in organ culture. SiRNA 4 was chosen as the most efficient from four synthesized Smo siRNAs. Palatal shelf fusion rate of 4 μg/mL cyclopamine group was the lowest and significantly lower than that of blank control group (P<0.05), and that of siRNA 4 group was also lower than that of blank control group (P=0.183). At 48 h after transfection, Smo protein level of siRNA 4 gr...
Source: Biomedical and Environmental Sciences - September 12, 2016 Category: Biomedical Science Source Type: research
Phase 2 open-label extension study of patisiran, an investigational siRNA agent for hereditary ATTR amyloidosis with polyneuropathy (hATTR-PN)
Hereditary ATTR amyloidosis with polyneuropathy (hATTR-PN), also known as familial amyloidotic polyneuropathy (FAP), is an inherited, progressive disease that can cause sensory, motor, and autonomic dysfunction, resulting in significant disability and death. Patisiran is an investigational, systemically administered small interfering RNA (siRNA) targeting wild-type and mutant TTR. A recently completed multi-center, multi-dose Phase 2 trial of patisiran in hATTR-PN patients (N = 29) showed>80% sustained mean knockdown of serum TTR when administered at a dose of 0.3 mg/kg every 3 weeks with a generally favorable safety profile.
Source: Neuromuscular Disorders - September 10, 2016 Category: Neurology Authors: I. Conceicao, O. Suhr, T. Coelho, M. Waddington Cruz, H. Schmidt, J. Buades, J. Campistol, J. Pouget, J. Berk, D. Adams Source Type: research
The inhibition of epidermal growth factor receptor signaling by hexagonal selenium nanoparticles modified by SiRNA
Source: Cancer Gene Therapy - September 8, 2016 Category: Cancer & Oncology Authors: L Kamrani Moghaddam S Ramezani Paschepari M A Zaimy A Abdalaian A Jebali Source Type: research
Mapping Optimal Charge Density and Length of ROMP-based PTDMs for siRNA Internalization.
Abstract A fundamental understanding of how polymer structure impacts internalization and delivery abilities of biologically relevant cargoes, particularly siRNA, is of critical importance to the successful design of improved delivery reagents. Herein we report the use of ring-opening metathesis polymerization (ROMP) methods to synthesize two series of guanidinium-rich protein transduction domain mimics (PTDMs): one based on an imide scaffold that contains one guanidinium moiety per repeat unit and another based on a diester scaffold that contains two guanidinium moieties per repeat unit. By varying both the degre...
Source: Biomacromolecules - September 5, 2016 Category: Biochemistry Authors: Caffrey LM, deRonde BM, Minter LM, Tew GN Tags: Biomacromolecules Source Type: research
Ultrasound-targeted microbubble destruction of calcium channel subunit α 1D siRNA inhibits breast cancer via G protein-coupled receptor 30.
In conclusion, E2 upregulated the expression of Cav1.3 for Ca2+ influx to promote the expression of p-ERK1/2 for cell proliferation. The study confirmed that the mechanism of E2 inducing the expression of Cav1.3 through a non-genomic pathway, and highlighted that UTMD of Cav1.3 siRNA is a powerful promising technology for breast cancer gene therapy. PMID: 27572936 [PubMed - as supplied by publisher]
Source: Oncology Reports - September 1, 2016 Category: Cancer & Oncology Tags: Oncol Rep Source Type: research
Impact of siRNA targeting of β-catenin on differentiation of rat neural stem cells and gene expression of Ngn1 and BMP4 following in vitro hypoxic-ischemic brain damage.
Authors: Zhang X, Zhu C, Luo Q, Dong J, Liu L, Li M, Zhu H, Ma X, Wang J Abstract The aim of the present study was to investigate the possible damage-repair mechanisms of neural stem cells (NSCs) following hypoxic-ischemic brain damage (HIBD). NSCs obtained from Sprague Dawley rats were treated with tissue homogenate from normal or HIBD tissue, and β‑catenin expression was silenced using siRNA. The differentiation of NSCs was observed by immunofluorescence, and semiquantitative reverse transcription‑polymerase chain reaction and western blot analysis were applied to detect the mRNA and protein expression level...
Source: Molecular Medicine Reports - September 1, 2016 Category: Molecular Biology Tags: Mol Med Rep Source Type: research
Silencing Aurora-A with siRNA inhibits cell proliferation in human lung adenocarcinoma cells.
In this study, we investigated the expression of AURKA in lung adenocarcinoma tissues, the role of small interference RNA targeting AURKA on growth, cell cycle, and apoptosis of lung adenocarcinoma cell lines in vitro. The AURKA is highly expressed in lung adenocarcinoma tissues and human lung adenocarcinoma cell lines. Lentivirus-mediated short hairpin RNA (shRNA) was used to knock down AURKA expression in human lung adenocarcinoma cell lines H1299 and A549. The results indicated that depletion of AURKA could inhibit cell growth, cause cell cycle arrest and apoptosis. The potential mechanisms of AURKA inhibition induced ...
Source: International Journal of Oncology - August 31, 2016 Category: Cancer & Oncology Authors: Zhong N, Shi S, Wang H, Wu G, Wang Y, Ma Q, Wang H, Liu Y, Wang J Tags: Int J Oncol Source Type: research
Quantum dot mediated delivery of siRNA to inhibit sphingomyelinase activities in brain ‐derived cells
This article is protected by copyright. All rights reserved.
Source: Journal of Neurochemistry - August 31, 2016 Category: Neuroscience Authors: T Getz, J Qin, I L Medintz, J B Delehanty, K Susumo, P E Dawson, G Dawson Tags: Original Article Source Type: research
PEGylation of lipoplexes: The right balance between cytotoxicity and siRNA effectiveness.
In conclusion, the right balance between cytotoxicity and siRNA effectiveness has been found with the transfection of lipoplexes coated with 20% of Ceramide-PEG2000. This new nanovector could have a high potential against multiple mucosal diseases, such as human papillomavirus-induced genital lesions. PMID: 27593989 [PubMed - as supplied by publisher]
Source: European Journal of Pharmaceutical Sciences - August 31, 2016 Category: Drugs & Pharmacology Authors: Lechanteur A, Furst T, Evrard B, Delvenne P, Hubert P, Piel G Tags: Eur J Pharm Sci Source Type: research
An siRNA screen for ATG protein depletion reveals the extent of the unconventional functions of the autophagy proteome in virus replication
Autophagy is a catabolic process regulated by the orchestrated action of the autophagy-related (ATG) proteins. Recent work indicates that some of the ATG proteins also have autophagy-independent roles. Using an unbiased siRNA screen approach, we explored the extent of these unconventional functions of ATG proteins. We determined the effects of the depletion of each ATG proteome component on the replication of six different viruses. Our screen reveals that up to 36% of the ATG proteins significantly alter the replication of at least one virus in an unconventional fashion. Detailed analysis of two candidates revealed an undo...
Source: Journal of Cell Biology - August 28, 2016 Category: Cytology Authors: Mauthe, M., Langereis, M., Jung, J., Zhou, X., Jones, A., Omta, W., Tooze, S. A., Stork, B., Paludan, S. R., Ahola, T., Egan, D., Behrends, C., Mokry, M., de Haan, C., van Kuppeveld, F., Reggiori, F. Tags: Cell Death and Autophagy, Virology Tools Source Type: research
Lipophilic 2'-O-Acetalester RNAs:Synthesis, Thermal Duplex Stability, Nuclease Resistance, Cellular Uptake and siRNA Activity after Spontaneous Naked Delivery.
We report synthesis, biochemical and biophysical characteristics of 2'-O-phenylisobutyryloxymethyl (PiBuOM)-modified siRNA and their impact on biological activity. In case of spontaneous cellular uptake of naked PiBuOM-modified siRNA, we observe increased target suppression in human cells versus unmodified or pivaloyloxymethyl (PivOM)-modified siRNA. We provide evidence for improved spontaneous cellular uptake of naked PiBuOM-modified siRNA and for substantial target suppression in human cells in serum-containing medium. PMID: 27569765 [PubMed - as supplied by publisher]
Source: Chembiochem - August 28, 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
Folate-targeted amphiphilic cyclodextrin.siRNA nanoparticles for prostate cancer therapy exhibit PSMA mediated uptake, therapeutic gene silencing in vitro and prolonged circulation in vivo
This study highlights the ability of incorporating a folate ligand into CD.siRNA nanoparticles to allow for targeted delivery of siRNA to prostate cancer cells via the PSMA. Graphical abstract
Source: Nanomedicine: Nanotechnology, Biology and Medicine - August 27, 2016 Category: Nanotechnology Source Type: research
A Focused Library Approach to Discover Discrete Dipeptide Bolaamphiphiles for siRNA Delivery.
In this study, we report a new dipeptide functionalization strategy for developing new dendritic bolaamphiphile vectors for efficient siRNA transfection. A focused library of dipeptides was constructed using four amino acids: L-arginine, L-histidine, L-lysine and L-tryptophan. The dipeptides were coupled to two dendritic bolaamphiphile scaffolds that we developed previously, allowing us to quickly access a focused library of discrete vectors with multivalent dendritic dipeptide functionalities. The resulting discrete bolaamphiphiles were screened for siRNA delivery in vitro in HEK-293 and HeLa cells. Bolaamphiphiles functi...
Source: Biomacromolecules - August 25, 2016 Category: Biochemistry Authors: Eldredge AC, Johnson ME, Oldenhuis NJ, Guan Z Tags: Biomacromolecules Source Type: research
CD25 siRNA induces Treg/Th1 cytokine expression in rat corneal transplantation models.
In conclusion, CD25 siRNA gene therapy played a protective role in corneal graft rejection via up-regulation of Treg cytokine expression and down-regulation of Th1 cytokine expression. PMID: 27567557 [PubMed - as supplied by publisher]
Source: Experimental Eye Research - August 23, 2016 Category: Opthalmology Authors: Qin Q, Luo D, Shi Y, Zhao Q, Chen Y, Wu J, Zhao M Tags: Exp Eye Res Source Type: research
Application of bifurcation theory and siRNA-based control signal to restore the proper response of cancer cells to DNA damage
Publication date: 7 November 2016 Source:Journal of Theoretical Biology, Volume 408 Author(s): Emilia Kozłowska, Krzysztof Puszynski Many diseases with a genetic background such as some types of cancer are caused by damage in the p53 signaling pathway. The damage changes the system dynamics providing cancer cells with resistance to therapy such as radiation therapy. The change can be observed as the difference in bifurcation diagrams and equilibria type and location between normal and damaged cells, and summarized as the changes of the mathematical model parameters and following changes of the eigenvalues of Jacobian mat...
Source: Journal of Theoretical Biology - August 23, 2016 Category: Biology Source Type: research
Liposome-polyethylenimine complexes (DPPC-PEI lipopolyplexes) for therapeutic siRNA delivery in vivo
Therapeutic applications of RNA interference (RNAi) require efficient siRNA delivery strategies in vivo. Combining lipid-based carriers with polymeric nanoparticles offers the favourable properties of both systems. This is the first study to explore polyethylenimine-based lipopolyplexes comprising a low-molecular weight PEI and the phospholipid DPPC for therapeutic siRNA use. Lipopolyplex structures are analysed by electron microscopy. Biological efficacies are demonstrated in vitro by cellular uptake, knockdown of the target oncogene survivin and concomitant cell growth inhibition.
Source: Nanomedicine : Nanotechnology, Biology, and Medicine - August 20, 2016 Category: Nanotechnology Authors: Alexander Ewe, Omkar Panchal, Shashank Reddy Pinnapireddy, Udo Bakowsky, Susanne Przybylski, Achim Temme, Achim Aigner Source Type: research
Validation of a network-based strategy for the optimization of combinatorial target selection in breast cancer therapy: siRNA knockdown of network targets in MDA-MB-231 cells as an in vitro model for inhibition of tumor development.
Authors: Tilli TM, Carels N, Tuszynski JA, Pasdar M Abstract Network-based strategies provided by systems biology are attractive tools for cancer therapy. Modulation of cancer networks by anticancer drugs may alter the response of malignant cells and/or drive network re-organization into the inhibition of cancer progression. Previously, using systems biology approach and cancer signaling networks, we identified top-5 highly expressed and connected proteins (HSP90AB1, CSNK2B, TK1, YWHAB and VIM) in the invasive MDA-MB-231 breast cancer cell line. Here, we have knocked down the expression of these proteins, individua...
Source: Oncotarget - August 18, 2016 Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Nanoparticle-mediated siRNA delivery assessed in a 3D co-culture model simulating prostate cancer bone metastasis
This study aimed to develop and characterise a 3D in vitro co-culture model to simulate prostate cancer bone metastasis and to assess the ability of the model to investigate nanoparticle-mediated siRNA delivery and gene knockdown. PC3 or LNCaP prostate cancer cells were co-cultured with hFOB 1.19 osteoblast cells in 2D on plastic tissue culture plates and in 3D on collagen scaffolds mimicking the bone microenvironment. To characterise the co-culture model, cell proliferation, enzyme secretion and the utility of two different gene delivery vectors to mediate siRNA uptake and gene knockdown were assessed. Cell proliferation ...
Source: International Journal of Pharmaceutics - August 17, 2016 Category: Drugs & Pharmacology Source Type: research
Hepatic Stellate Cells in Liver Fibrosis and siRNA-Based Therapy.
Abstract Hepatic fibrosis is a reversible wound-healing response to either acute or chronic liver injury caused by hepatitis B or C, alcohol, and toxic agents. Hepatic fibrosis is characterized by excessive accumulation and reduced degradation of extracellular matrix (ECM). Excessive accumulation of ECM alters the hepatic architecture leading to liver fibrosis and cirrhosis. Cirrhosis results in failure of common functions of the liver. Hepatic stellate cells (HSC) play a major role in the development of liver fibrosis as HSC are the main source of the excessive production of ECM in an injured liver. RNA interfere...
Source: Pharmacological Reviews - August 17, 2016 Category: Drugs & Pharmacology Authors: Omar R, Yang J, Liu H, Davies NM, Gong Y Tags: Rev Physiol Biochem Pharmacol Source Type: research
Dual-functionalized graphene oxide for enhanced siRNA delivery to breast cancer cells
Publication date: 1 November 2016 Source:Colloids and Surfaces B: Biointerfaces, Volume 147 Author(s): Rana Imani, Wei Shao, Samira Taherkhani, Shahriar Hojjati Emami, Satya Prakash, Shahab Faghihi The aim of this study is to improve hydrocolloid stability and siRNA transfection ability of a reduced graphene oxide (rGO) based nano-carrier using a phospholipid-based amphiphilic polymer (PL-PEG) and cell penetrating peptide (CPPs). The dual functionalized nano-carrier is comprehensively characterized for its chemical structure, size, surface charge and morphology as well as thermal stability. The nano-carrier cytocompatibil...
Source: Colloids and Surfaces B: Biointerfaces - August 17, 2016 Category: Biochemistry Source Type: research
Enhancing radiosensitivity of TE1, TE8, and TE 11 esophageal squamous carcinoma cell lines by Hdm2-siRNA targeted gene therapy in vitro.
CONCLUSION: Increasing radiosensitivity of tumor cells may be provided by silencing the oncogenes. PMID: 27525226 [PubMed]
Source: BioImpacts - August 16, 2016 Category: Research Tags: Bioimpacts Source Type: research
Overcoming the challenges of siRNA delivery: Nanoparticle strategies.
Abstract RNA interference (RNAi) is a natural cellular process that can be operated to silence specific genes expression in post-transcriptional level by intracellular delivery of small interfering RNAs (siRNAs) and microRNAs. Therapeutics based on siRNA have an immense potential for the treatment of incurable diseases such as cancers. However, the in vivo utilization of siRNA and also the delivery of this agent to the target site is one of the most controversial challenges, the helpful assistance by nanoparticles can improve stable delivery and also enhance efficacy. More nanoparticle-based siRNA therapeutics is ...
Source: Current Drug Delivery - August 15, 2016 Category: Drugs & Pharmacology Authors: Shajari N, Mansoori B, Davudian S, Mohammadi A, Baradaran B Tags: Curr Drug Deliv Source Type: research
Nek2 siRNA therapy using a portal venous port –catheter system for liver metastasis in pancreatic cancer
In this study, the overexpression of Nek2 was identified in pancreatic cancer cell lines. Nek2 siRNA inhibited tumor growth in a subcutaneous xenograft mouse model of pancreatic cancer, prolonged the survival time in an intraperitoneal xenograft mouse model and efficiently prevented the progression of liver metastasis using a portal venous port–catheter system. Taken together, Nek2 is an effective therapeutic target in pancreatic cancer. An adequate delivery system is considered important in treating advanced pancreatic cancer, such as peritoneal dissemination and liver metastasis. Further investigations are required on ...
Source: Cancer Science - August 11, 2016 Category: Cancer & Oncology Authors: Toshio Kokuryo, Shigeru Hibino, Kazushi Suzuki, Katsutaka Watanabe, Yukihiro Yokoyama, Masato Nagino, Takeshi Senga, Michinari Hamaguchi Tags: Original Article Source Type: research
Dual-functionalized graphene oxide for enhanced siRNA delivery to breast cancer cells.
Abstract The aim of this study is to improve hydrocolloid stability and siRNA transfection ability of a reduced graphene oxide (rGO) based nano-carrier using a phospholipid-based amphiphilic polymer (PL-PEG) and cell penetrating peptide (CPPs). The dual functionalized nano-carrier is comprehensively characterized for its chemical structure, size, surface charge and morphology as well as thermal stability. The nano-carrier cytocompatibility, siRNA condensation ability both in the presence and absence of enzyme, endosomal buffering capacity, cellular uptake and intracellular localization are also assessed. The siRNA...
Source: Colloids and Surfaces - August 11, 2016 Category: Biotechnology Authors: Imani R, Shao W, Taherkhani S, Emami SH, Prakash S, Faghihi S Tags: Colloids Surf B Biointerfaces Source Type: research
Smart inulin-based polycationic nanodevices for siRNA delivery.
Abstract The advances of short interfering RNA (siRNA) mediated therapy provide a powerful option for treatment of many diseases by silencing the expression of targeted genes including cancer development and progression. Inulin is a very simple and biocompatible polysaccharide proposed by our groups to produce interesting delivery systems for Nucleic acid based drugs (NABDs), such as siRNA, either as polycations able to give polyplexes and polymeric coatings for nanosystems having a metallic core. In this research field different functionalizing groups were linked to the inulin backbone with specific aims includin...
Source: Current Drug Delivery - August 10, 2016 Category: Drugs & Pharmacology Authors: Lamberti G, Cavallaro G, Sardo C, Scialabba C, Licciardi M, Giammona G Tags: Curr Drug Deliv Source Type: research
A Chromatin-Focused siRNA Screen for Regulators of p53-Dependent Transcription
The protein product of the Homo sapiens TP53 gene is a transcription factor (p53) that regulates the expression of genes critical for the response to DNA damage and tumor suppression, including genes involved in cell cycle arrest, apoptosis, DNA repair, metabolism, and a number of other tumorigenesis-related pathways. Differential transcriptional regulation of these genes is believed to alter the balance between two p53-dependent cell fates: cell cycle arrest or apoptosis. A number of previously identified p53 cofactors covalently modify and alter the function of both the p53 protein and histone proteins. Both gain- and lo...
Source: G3: Genes Genomes Genetics - August 8, 2016 Category: Genetics & Stem Cells Authors: Sammons, M. A., Zhu, J., Berger, S. L. Tags: Mutant Screen Report Source Type: research
LncRNA NONRATT021972 siRNA rescued decreased heart rate variability in diabetic rats in superior cervical ganglia.
Abstract Diabetic cardiac autonomic neuropathy (DCAN) is a serious and common complication in diabetes mellitus (DM). Long noncoding RNAs (lncRNAs), an important class of regulatory molecules in diverse biological processes, have attracted considerable interest in DCAN. Our previous study has indicated a lncRNA, NONRATT021972 (NONCODE ID), was enhanced in sympathetic neuronal-like PC12 cells in the setting of high glucose (HG) and high FFAs (HF); its silence was found to significantly alleviate HGHF-induced tumor necrosis factor-α (TNF-α) release in PC12 cells. Here we further explore the effects of NONRATT02197...
Source: Autonomic Neuroscience - August 4, 2016 Category: Neuroscience Authors: Xu H, Liu C, Rao S, He L, Zhang T, Sun S, Wu B, Zou L, Wang S, Xue Y, Jia T, Zhao S, Li G, Liu S, Li G, Liang S Tags: Auton Neurosci Source Type: research
Effect of Smo SiRNA-mediated Hedgehog Signaling Pathway Inhibition on Palatal Fusion.
Abstract We used Smo siRNA to inhibit hedgehog signaling pathway in embryonic day (E) 13 palatal shelves in organ culture. SiRNA 4 was chosen as the most efficient from four synthesized Smo siRNAs. Palatal shelf fusion rate of 4 μg/mL cyclopamine group was the lowest and significantly lower than that of blank control group (P<0.05), and that of siRNA 4 group was also lower than that of blank control group (P=0.183). At 48 h after transfection, Smo protein level of siRNA 4 group was 64.8% lower than that of blank control group (P<0.05), and Gli1 protein level of 4 μg/mL cyclopamine group was 68.9% lower tha...
Source: Biomedical and Environmental Sciences : BES - July 31, 2016 Category: Biomedical Science Authors: Zhou Q, Wu HF, Wei Y, Zhu WL Tags: Biomed Environ Sci Source Type: research