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Total 77 results found since Jan 2013.

Current Development of siRNA Bioconjugates: From Research to the Clinic
In this study, it was shown that the main factor determining the nature of the biodistribution of conjugates is their lipophilicity. Conjugates of siRNA with lower lipophilicity; i.e., derivatives of retinoic acid, lithocholic acid, and docosahexanoic acid with greater efficiency than cholesterol conjugates accumulated in the kidneys, bladder, and lungs of the mouse after subcutaneous injection (Biscans et al., 2018). This fact is consistent with previous data that showed that more lipophilic conjugates bind more efficiently to serum components, and thus are not excreted by the kidneys (Wolfrum et al., 2007; Osborn et al.,...
Source: Frontiers in Pharmacology - April 25, 2019 Category: Drugs & Pharmacology Source Type: research

Engineered targeting tLyp-1 exosomes as gene therapy vectors for efficient delivery of siRNA into lung cancer cells
In conclusion, the targeting tLyp-1 exosomes are successfully engineered, and can be used for gene therapy with a high transfection efficiency. Therefore, the engineered targeting tLyp-1 exosomes offer a promising gene delivery platform for future cancer therapy.Graphical AbstractThe tLyp-1-lamp2b plasmid transfected HEK293T cells can secreted tumor targeting tLyp-1 exosomes. By electroporation technology, targeting tLyp-1 exosomes were loaded with siRNA. When targeting tLyp-1 exosome ruptured in cytoplasm, siRNA was loaded into the RNA-induced silencing complex (RISC). The sense (passenger) strand was degraded while the a...
Source: Asian Journal of Pharmaceutical Sciences - May 8, 2019 Category: Drugs & Pharmacology Source Type: research

Well-defined cationic N-3-(dimethylamino)propylmethacrylamide hydrochloride based (co)polymers for siRNA delivery.
Abstract Cationic glycopolymers have shown to be excellent candidates for the fabrication of gene delivery devices due to their ability to electrostatically interact with negatively charged nucleic acids and the carbohydrate residues ensure enhanced stability and low toxicity of the polyplexes. The ability to engineer the polymers for optimized compositions, molecular weights and architectures is critical in the design of effective gene delivery vehicles. Therefore, in this study, the aqueous reversible addition-fragmentation chain transfer polymerization (RAFT) was used to synthesize well-defined cationic glycopo...
Source: Biomacromolecules - December 1, 2017 Category: Biochemistry Authors: Singhsa P, Diaz-Dussan D, Manuspiya H, Narain R Tags: Biomacromolecules Source Type: research

Synthesis, RNAi activity and nuclease-resistant properties of apolar carbohydrates siRNA conjugates.
Abstract Oligoribonucleotide conjugates carrying apolar carbohydrates at the 5'-end and the corresponding siRNA duplexes have been prepared using phosphoramidite chemistry. All the carbohydrate-siRNA derivatives were compatible with RNA interference machinery if transfected with oligofectamine. In the absence of a transfection agent, some of them exerted certain reduction of gene expression. Double-tailed permethylated glucose conjugated to siRNA through a long spacer inhibited gene expression up to 26% compared to the scrambled duplex. Such modifications contribute positively to the stability of oligoribonucleoti...
Source: Bioorganic and Medicinal Chemistry Letters - May 28, 2013 Category: Chemistry Authors: Vengut-Climent E, Terrazas M, Lucas R, Arévalo-Ruiz M, Eritja R, Morales JC Tags: Bioorg Med Chem Lett Source Type: research

GABAB receptor ligand-directed trimethyl chitosan/tripolyphosphate nanoparticles and their pMDI formulation for survivin siRNA pulmonary delivery
Publication date: 1 January 2018 Source:Carbohydrate Polymers, Volume 179 Author(s): Suhui Ni, Yun Liu, Yue Tang, Jing Chen, Shuhan Li, Ji Pu, Lidong Han The effect of gene silencing by survivin siRNA (siSurvivin) on the proliferation and apoptosis of lung tumor has been attracted more interest. GABAB receptor ligand-directed nanoparticles consisting of baclofen functionalized trimethyl chitosan (Bac-TMC) as polymeric carriers, tripolyphosphate (TPP) as ionic crosslinker, and siSurvivin as therapeutic genes, were designed to enhance the survivin gene silencing. GABAB receptor agonist baclofen (Bac) was initially introduce...
Source: Carbohydrate Polymers - October 2, 2017 Category: Biomedical Science Source Type: research

Genes, Vol. 9, Pages 74: Covalent Strategies for Targeting Messenger and Non-Coding RNAs: An Updated Review on siRNA, miRNA and antimiR Conjugates
Eritja Oligonucleotide-based therapy has become an alternative to classical approaches in the search of novel therapeutics involving gene-related diseases. Several mechanisms have been described in which demonstrate the pivotal role of oligonucleotide for modulating gene expression. Antisense oligonucleotides (ASOs) and more recently siRNAs and miRNAs have made important contributions either in reducing aberrant protein levels by sequence-specific targeting messenger RNAs (mRNAs) or restoring the anomalous levels of non-coding RNAs (ncRNAs) that are involved in a good number of diseases including cancer. In addition t...
Source: Genes - February 6, 2018 Category: Genetics & Stem Cells Authors: Santiago Grijalvo Adele Alagia Andreia Jorge Ramon Eritja Tags: Review Source Type: research

Glycosylated RAFT polymers with varying PEG linkers produce different siRNA uptake, gene silencing and toxicity profiles.
Abstract Achieving efficient and targeted delivery of short interfering (siRNA) is an important research challenge to overcome to render highly promising siRNA therapies clinically successful. Challenges exist in designing synthetic carriers for these RNAi constructs that provide protection against serum degradation, extended blood retention times, effective cellular uptake through a variety of uptake mechanisms, endosomal escape and efficient cargo release. These challenges have resulted in a significant body of research, and led to many important findings about the chemical composition and structural layout of t...
Source: Biomacromolecules - October 23, 2017 Category: Biochemistry Authors: Williams EGL, Hutt OE, Hinton TM, Larnaudie SC, Le T, MacDonald JM, Gunatillake P, Thang SH, Duggan PJ Tags: Biomacromolecules Source Type: research

Amphipathic Chitosans Improve the Physicochemical Properties of siRNA-Chitosan Nanoparticles at Physiological Conditions
In this study, a series of amphipathic chitosans were synthesized by varying the degree of acetylation (DA) from ˜2 to ˜30 mol% and the degree of substitution (DS) from 5 to 25%. by tertiary amino groups (DEAE) The results showed that the adjustment of these parameters decreases the interparticle interactions mediated by hydrogen bonding to obtain nanoparticles with improved colloidal stability. siRNA-containing nanoparticles of 100 to 150 nm with low polydispersities (0.15-0.2) and slightly positive zeta potentials (˜ + 5 mV) were resistant to aggregation at pH 7.4 and ionic strength of 150 mM. This resista...
Source: Carbohydrate Polymers - March 29, 2019 Category: Biomedical Science Source Type: research

Cell-selective siRNA delivery using glycosylated dynamic covalent polymers self-assembled in situ by RNA-templating.
Abstract Dynamic covalent libraries enable exploring complex chemical systems from which bioactive assemblies can adaptively emerge through template effects. In this work, we studied dynamic covalent libraries made of complementary bifunctional cationic peptides, yielding a diversity of species from macrocycles to polymers. Although polymers are typically expressed only at high concentration, we found that siRNA act as a template in the formation of dynamic covalent polymers at low concentration in a process guided by electrostatic binding. Using a glycosylated building block, we were able to show that this templa...
Source: Angewandte Chemie - December 8, 2020 Category: Chemistry Authors: Laroui N, Coste M, Su D, Ali L, Bessin Y, Barboiu M, Gary-Bobo M, Bettache N, Ulrich S Tags: Angew Chem Int Ed Engl Source Type: research

Preparation and Cell Activities of Lactosylated Curdlan-triornithine Nanoparticles for Enhanced DNA/siRNA Delivery in Hepatoma Cells
Publication date: Available online 27 August 2019Source: Carbohydrate PolymersAuthor(s): Xia Wang, Yuxuan Qi, Lixia Liu, Tsogzolmaa Ganbold, Huricha Baigude, Jingfen HanAbstractA long-anticipated cancer therapy would deliver the right type of therapeutic agents to the target in control with minimal systemic toxicity. The purpose of this study was to prepare lactosylated curdlan-triornithine nanocarriers (CTOLs), and target deliver gene to hepatoma cells. Structures and biophysical properties had been elucidated with physical and chemical methods. The results revealed that those functionalized polymers can completely conden...
Source: Carbohydrate Polymers - August 28, 2019 Category: Biomedical Science Source Type: research

Genetic Regulation of Liver Metabolites and Transcripts Linking to Biochemical-Clinical Parameters
Conclusion In summary, this study is the first to combine metabolomics, transcriptomics, and genome-wide association studies in a porcine model. Our results improve understanding of the genetic regulation of metabolites which link to transcripts and finally biochemical-clinical parameters. Further, high-performance profiling of metabolites as intermediate phenotypes is a potentially powerful approach to uncover how genetic variation affects metabolic and health status. Our results advance knowledge in areas of biomedical and agricultural interest and identify potential correlates of biomarkers, SNPs-metabolites, SNPs-tran...
Source: Frontiers in Genetics - April 16, 2019 Category: Genetics & Stem Cells Source Type: research

Oligonucleotides —A Novel Promising Therapeutic Option for IBD
Conclusions In this review, we focused on recent and past approaches to test the therapeutic efficacy of oligonucleotide based therapies in IBD. The combining mechanistic mode of oligonucleotide based therapeutics is a targeted action on specific pro-inflammatory molecules, which are over activated in IBD patients and contribute significantly to disease pathogenesis. The proposed high selectivity of the agents is derived from its mode of action, that aims to specifically block certain inflammatory molecular patterns, without a general systemic effect on other molecular targets. It would be important for each oligonucleot...
Source: Frontiers in Pharmacology - April 23, 2019 Category: Drugs & Pharmacology Source Type: research

Complement C5b-9 and Cancer: Mechanisms of Cell Damage, Cancer Counteractions, and Approaches for Intervention
In conclusion, osmotic burst of inflated complement-damaged cells may occur, but these bursts are most likely a consequence of metabolic collapse of the cell rather than the cause of cell death. The Complement Cell Death Mediator: A Concerted Action of Toxic Moieties Membrane pores caused by complement were first visualized by electron microscopy on red blood cell membranes as large ring structures (22). Similar lesions were viewed on E. coli cell walls (23). Over the years, ample information on the fine ultrastructure of the MAC that can activate cell death has been gathered (24) and has been recently further examined (...
Source: Frontiers in Immunology - April 9, 2019 Category: Allergy & Immunology Source Type: research

Receptor-mediated delivery of therapeutic RNA by peptide functionalized curdlan nanoparticles.
Abstract Natural carbohydrate polymer-based nanoparticles have great biocompatibility that is required for the safe delivery of various drugs including nucleic acid therapeutics. Herein, we designed curdlan-based nanoparticles for cancer cell targeted delivery of short interfering RNA (siRNA). iRGD peptide conjugated 6-amino-6-deoxy curdlan specifically delivered siRNA to integrin expressing cancer cells. Incubation of cancer cells with free iRGD peptide competitively blocked cellular uptake of the iRGD functionalized curdlan nanoparticles. Chloroquine but not nystatin inhibited cellular uptake of iRGD functionali...
Source: International Journal of Biological Macromolecules - December 17, 2018 Category: Biochemistry Authors: Ganbold T, Han S, Hasi A, Baigude H Tags: Int J Biol Macromol Source Type: research

Chitosan-Mediated shRNA Knockdown of Cytosolic Alanine Aminotransferase Improves Hepatic Carbohydrate Metabolism.
In this study, we examined the effect of silencing cytosolic ALT (cALT) expression on the hepatic metabolism in Sparus aurata. A number of siRNA and shRNA designed to down-regulate cALT expression were validated in HEK-293 cells transfected with plasmids expressing S. aurata cALT or mitochondrial ALT (mALT) isoforms: ALT silencing significantly decreased the expression levels of S. aurata mRNA cALT1 to 62 % (siRNA) and 48 % (shRNA) of the values observed in control cells. The effect of cALT silencing was analysed in the liver of S. aurata 72 h after intraperitoneal injection of chitosan-tripolyphosphate (TPP) nanopartic...
Source: Marine Biotechnology - October 16, 2015 Category: Biotechnology Authors: González JD, Silva-Marrero JI, Metón I, Caballero-Solares A, Viegas I, Fernández F, Miñarro M, Fàbregas A, Ticó JR, Jones JG, Baanante IV Tags: Mar Biotechnol (NY) Source Type: research