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siRNA-Mediated RNA Interference in Precision-Cut Tissue Slices Prepared from Mouse Lung and Kidney
In conclusion, thisex vivo transfection model can be used to evaluate the effects of siRNA in relevant biological environments.
Source: The AAPS Journal - September 11, 2017 Category: Drugs & Pharmacology Source Type: research

The pH-Triggered Triblock Nanocarrier Enabled Highly Efficient siRNA Delivery for Cancer Therapy
Small interfering RNA (siRNA) therapies have been hampered by lack of delivery systems in the past decades. Nowadays, a few promising vehicles for siRNA delivery have been developed and it is gradually revealed that enhancing siRNA release from endosomes into cytosol is a very important factor for successful delivery. Here, we designed a novel pH-sensitive nanomicelle, PEG-PTTMA-P(GMA-S-DMA) (PTMS), for siRNA delivery. Owing to rapid hydrolysis in acidic environment, PTMS NPs underwent hydrophobic-to-hydrophilic transition in endosomes that enabled combination of proton sponge effect and raised osmotic pressure in endosome...
Source: Theranostics - September 12, 2017 Category: Molecular Biology Authors: Lili Du, Junhui Zhou, Lingwei Meng, Xiaoxia Wang, Changrong Wang, Yuanyu Huang, Shuquan Zheng, Liandong Deng, Huiqing Cao, Zicai Liang, Anjie Dong, Qiang Cheng Tags: Research Paper Source Type: research

Dual-responsive polyplexes with enhanced disassembly and endosomal escape for efficient delivery of siRNA.
Abstract Despite the extracellular barriers for siRNA delivery have been overcome by utilizing advanced nanoparticle delivery systems, the key intracellular barriers after internalization including efficient disassembly of siRNA and endosomal escape still remains challenging. To address the issues, we developed a unique pH- and redox potential-responsive polyplex delivery system based on the copolymer of mPEG-b-PLA-PHis-ssPEI1.8 k, which is composed of a pH-responsive copolymer of PEG-b-PLA-PHis (Mw 5 k) and a branched PEI (Mw1.8 k) linked with redox cleavable disulfide bond. The copolymer showed excellent s...
Source: Biomaterials - February 3, 2018 Category: Materials Science Authors: Zhu J, Qiao M, Wang Q, Ye Y, Ba S, Ma J, Hu H, Zhao X, Chen D Tags: Biomaterials Source Type: research

Preparation of PEGylated cationic nanoliposome-siRNA complexes for cancer therapy.
In conclusion, our novel PEGylated liposomes have high potential for systemic delivery of siRNA and can improve in vivo stability of free siRNA and also siRNA lipoplexes. PMID: 29475393 [PubMed - as supplied by publisher]
Source: Artificial Cells, Nanomedicine and Biotechnology - February 26, 2018 Category: Biotechnology Tags: Artif Cells Nanomed Biotechnol Source Type: research

Protective effect of Gelofusine against cRGD-siRNA-induced nephrotoxicity in mice.
Authors: Liao W, Qin Y, Liao L, Cen B, Wu Z, Wei Y, Wang Z, Li G, Ji A Abstract Based on successful targeting to the αvβ3 integrin of cyclic arginine-glycine-aspartic acid (cRGD), cRGD-conjugated small interfering RNA (siRNA) exhibits tumor targeting and has become a new treatment strategy for solid tumors. However, the nephrotoxicity caused by its renal retention limits its clinical application. Here, we evaluated the protective effect of Gelofusine against cRGD-conjugated siRNA-induced nephrotoxicity in mice. Male Kunming mice (six per group) were either co-injected with Gelofusine and cRGD-siRNA or injected wi...
Source: Renal Failure - April 7, 2018 Category: Urology & Nephrology Tags: Ren Fail Source Type: research

Local Silencing of Connective Tissue Growth Factor by siRNA/Peptide Improves Dermal Collagen Arrangements
Conclusion:CTGF expression was down-regulated to 40% of control by CTGF siRNA/KALA (1:24) complexes (p <  0.01) and collagen lattice contraction was inhibited. However, down-regulated of CTGF by CTGF siRNA/MPG∆NLS complexes was not statistically significant. CTGF KALA-treated wound appeared with well formed-basket weave pattern of collagen fibrils with mean diameter of 128  ± 22 nm (n = 821). Mismatch siRNA/KALA-treated wound showed a high frequency of parallel small diameter fibrils (mean 90 ± 20 nm, n = 563).Conclusion:Controlling over-expression of CTGF by peptide-mediated siRNA delivery cou...
Source: Tissue Engineering and Regenerative Medicine - November 14, 2018 Category: Biotechnology Source Type: research

In vivo evaluation and Alzheimer's disease treatment outcome of siRNA loaded dual targeting drug delivery system.
Abstract To deliver drugs to treat Alzheimer's disease (AD), nanoparticles should firstly penetrate through blood brain barrier, and then target neurons. Recently, we developed an Apo A-I and NL4 dual modified nanoparticle (ANNP) to deliver beta-amyloid converting enzyme 1 (BACE1) siRNA. Although promising in vitro results were obtained, the in vivo performance was not clear. Therefore, in this study, we further evaluated the in vivo neuroprotective effect and toxicity of the ANNP/siRNA. The ANNP/siRNA was 80.6 nm with good stability when incubated with serum. The ANNP/siRNA could target both bEnd.3 and PC12 cells...
Source: Current Pharmaceutical Biotechnology - February 4, 2019 Category: Biotechnology Authors: Zhang C, Shen L, Gu Z, Liu X, Lin H Tags: Curr Pharm Biotechnol Source Type: research

i-Fect Scores Again
This study is the first to demonstrate that the stabilization of HIF1A expression underpins the development of bortezomib-induced neuropathic pain. Crucially, these findings reveal that the initiation and maintenance of bortezomib-induced neuropathic pain are regulated by distinct mechanisms.
Source: Neuromics - May 13, 2019 Category: Neuroscience Tags: chemotherapy i-Fect RNAi siRNA siRNA delivery in-vivo Source Type: news

Strategies, design, and chemistry in siRNA delivery systems.
Abstract Emerging therapeutics that utilize RNA interference (RNAi) have the potential to treat broad classes of diseases due to their ability to reversibly silence target genes. In August 2018, the FDA approved the first siRNA therapeutic, called ONPATTRO™ (Patisiran), for the treatment of transthyretin-mediated amyloidosis. This was an important milestone for the field of siRNA delivery that opens the door for additional siRNA drugs. Currently, >20 small interfering RNA (siRNA)-based therapies are in clinical trials for a wide variety of diseases including cancers, genetic disorders, and viral infections. T...
Source: Advanced Drug Delivery Reviews - May 14, 2019 Category: Drugs & Pharmacology Authors: Dong Y, Siegwart DJ, Anderson DG Tags: Adv Drug Deliv Rev Source Type: research

siRNA containing a unique 5-nucleotide motif acts as a quencher of IFI16-mediated innate immune response
Publication date: October 2019Source: Molecular Immunology, Volume 114Author(s): Hongyan Sui, Jun Yang, Xiaojun Hu, Qian Chen, Tomozumi ImamichiAbstractWe previously reported that some small interfering RNA (siRNA) enhances DNA or DNA virus mediated-interferon (IFN)-λ1(a type III IFN) induction through the crosstalk between retinoic acid-inducible gene I (RIG-I) and interferon gamma-inducible protein 16 (IFI16) signalling pathway. Here we provide further evidence of a new role for siRNA. siRNA containing a 5-nucleotide (nt) motif sequence suppresses DNA-mediated not only type III IFNs, but also type I IFNs and inflammator...
Source: Molecular Immunology - August 21, 2019 Category: Allergy & Immunology Source Type: research

siRNA therapeutics for breast cancer: recent efforts in targeting metastasis, drug resistance, and immune evasion.
Abstract Small interfering RNA (siRNA) has an established and precise mode of action to achieve protein knockdown. With the ability to target any protein, it is very attractive as a potential therapeutic for a plethora of diseases driven by the (over)expression of certain proteins. Utilizing siRNA to understand and treat cancer, a disease largely driven by genetic aberration, is thus actively investigated. However, the main hurdle for the clinical translation of siRNA therapeutics is to achieve effective delivery of siRNA molecules to tumors and the site of action, the cytosol, within cancer cells. Several nanopar...
Source: Translational Research : the journal of laboratory and clinical medicine - August 18, 2019 Category: Laboratory Medicine Authors: Ngamcherdtrakul W, Yantasee W Tags: Transl Res Source Type: research

Inhibitory effect of siRNA-Annexin A7 on growth, migration, and invasion in BGC823 cells and gastric cancer xenograftsin nude mice.
CONCLUSION: Gastric cancer xenografts were established in nude mice with human gastric cancer BGC823 cells. The volume and weight of tumor were decreased after inhibition of Annexin A7 expression in BGC823 cells. Tumor cells were arranged sparsely after inhibition of Annexin A7 expression in BGC823 cells. The siRNA-Annexin A7 inhibits Annexin A7 expression in transplanted gastric cancer of nude mice, and influences the growth, migration, and invasion of tumors by down-regulating the expression of PCNA and MMP-2, as well as up-regulating the expression of p27. PMID: 32211092 [PubMed]
Source: International Journal of Clinical and Experimental Pathology - March 28, 2020 Category: Pathology Authors: Yuan HF, Li Y, Tan BB, Zhao Q, Fan LQ, An ZJ Tags: Int J Clin Exp Pathol Source Type: research

Recent advances in siRNA delivery mediated by lipid-based nanoparticles.
Abstract Small interfering RNA (siRNA) has been expected to be a unique pharmaceutic for the treatment of broad-spectrum intractable diseases. However, its unfavorable properties such as easy degradation in the blood and negative-charge density are still a formidable barrier for clinical use. For disruption of this barrier, siRNA delivery technology has been significantly advanced in the past two decades. The approval of Patisiran (ONPATTRO™) for the treatment of transthyretin-mediated amyloidosis, the first approved siRNA drug, is a most important milestone. Since lipid-based nanoparticles (LNPs) are used in Pa...
Source: Advanced Drug Delivery Reviews - August 4, 2020 Category: Drugs & Pharmacology Authors: Yonezawa S, Koide H, Asai T Tags: Adv Drug Deliv Rev Source Type: research

siRNA potency enhancement via chemical modifications of nucleotide bases at the 5'-end of the siRNA guide strand.
Abstract Small interfering RNAs (siRNAs) can be utilized not only as functional biological research tools but also as therapeutic agents. For the clinical use of siRNA as drugs, various chemical modifications have been employed to improve the activity of siRNA drugs, and further chemical modifications are expected to improve the utility of siRNA therapeutics. As the 5' nucleobase of the guide strand affects the interaction between an siRNA and AGO2 and target cleavage activity, structural optimization of this specific position may be a useful strategy for improving siRNA activity. Here, using the in silico model o...
Source: RNA - November 11, 2020 Category: Genetics & Stem Cells Authors: Shinohara F, Oashi T, Harumoto T, Nishikawa T, Takayama Y, Miyagi H, Takahashi Y, Nakajima T, Sawada T, Koda Y, Makino A, Sato A, Hamaguch K, Suzuki M, Yamamoto J, Tomari Y, Saito JI Tags: RNA Source Type: research

The 2'-caged-tethered-siRNA shows light-dependent temporal controlled RNAi activity for GFP gene into HEK293T cells.
This report describes the syntheses of bulkier siRNA from 2'-caged-tethered-siRNAs, containing bulkier photolabile protecting group (o-nitrobenzyl) at 2'-position of ribose nucleoside. Importantly, these 2'-caged-siRNAs exhibit the light-dependent RNA interference (RNAi) activity into HEK293T cells for the GFP gene expression. The 2'-caged-siRNAs are synthesized by caging the sense and antisense strand of siRNA. The biochemical evaluations of these caged-siRNAs show that antisense-strand caged-siRNAs decrease RNAi activity temporarily in dark while enhancing RNAi activity, almost like control, after exposure withUV- light....
Source: Bioorganic and Medicinal Chemistry - December 9, 2020 Category: Chemistry Authors: Bollu A, Hassan MK, Dixit M, Sharma NK Tags: Bioorg Med Chem Source Type: research