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Total 63 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

Lipophilic siRNA targets albumin in situ and promotes bioavailability, tumor penetration, and carrier-free gene silencing Engineering
Clinical translation of therapies based on small interfering RNA (siRNA) is hampered by siRNA's comprehensively poor pharmacokinetic properties, which necessitate molecule modifications and complex delivery strategies. We sought an alternative approach to commonly used nanoparticle carriers by leveraging the long-lived endogenous serum protein albumin as an siRNA carrier. We synthesized...
Source: Proceedings of the National Academy of Sciences - August 8, 2017 Category: Science Authors: Samantha M. Sarett, Thomas A. Werfel, Linus Lee, Meredith A. Jackson, Kameron V. Kilchrist, Dana Brantley-Sieders, Craig L. Duvall Tags: PNAS Plus Source Type: research

Lipopeptides and selective siRNA delivery Engineering
siRNA therapeutics have promise for the treatment of a wide range of genetic disorders. Motivated by lipoproteins, we report lipopeptide nanoparticles as potent and selective siRNA carriers with a wide therapeutic index. Lead material cKK-E12 showed potent silencing effects in mice (ED50 ∼ 0.002 mg/kg), rats (ED50
Source: Proceedings of the National Academy of Sciences - March 18, 2014 Category: Science Authors: Dong, Y., Love, K. T., Dorkin, J. R., Sirirungruang, S., Zhang, Y., Chen, D., Bogorad, R. L., Yin, H., Chen, Y., Vegas, A. J., Alabi, C. A., Sahay, G., Olejnik, K. T., Wang, W., Schroeder, A., Lytton-Jean, A. K. R., Siegwart, D. J., Akinc, A., Barnes, C., Tags: Physical Sciences Source Type: research

Stability of siRNA on nanoparticle constructs Chemistry
Small interfering RNA (siRNA) is a powerful and highly effective method to regulate gene expression in vitro and in vivo. However, the susceptibility to serum nuclease-catalyzed degradation is a major challenge and it remains unclear whether the strategies developed to improve the stability of siRNA free in serum solution are...
Source: Proceedings of the National Academy of Sciences - July 8, 2014 Category: Science Authors: Barnaby, S. N., Lee, A., Mirkin, C. A. Tags: Physical Sciences Source Type: research

Structurally modulated codelivery of siRNA and Argonaute 2 for enhanced RNA interference Engineering
Small interfering RNA (siRNA) represents a promising class of inhibitors in both fundamental research and the clinic. Numerous delivery vehicles have been developed to facilitate siRNA delivery. Nevertheless, achieving highly potent RNA interference (RNAi) toward clinical translation requires efficient formation of RNA-induced gene-silencing complex (RISC) in the cytoplasm. Here we...
Source: Proceedings of the National Academy of Sciences - March 20, 2018 Category: Science Authors: Jiahe Li, Connie Wu, Wade Wang, Yanpu He, Elad Elkayam, Leemor Joshua-Tor, Paula T. Hammond Tags: PNAS Plus Source Type: research

Correction for Dong et al., Lipopeptide nanoparticles for potent and selective siRNA delivery in rodents and nonhuman primates Correction
ENGINEERING Correction for “Lipopeptide nanoparticles for potent and selective siRNA delivery in rodents and nonhuman primates,” by Yizhou Dong, Kevin T. Love, J. Robert Dorkin, Sasilada Sirirungruang, Yunlong Zhang, Delai Chen, Roman L. Bogorad, Hao Yin, Yi Chen, Arturo J. Vegas, Christopher A. Alabi, Gaurav Sahay, Karsten T. Olejnik, Weiheng...
Source: Proceedings of the National Academy of Sciences - April 15, 2014 Category: Science Tags: Corrections Source Type: research

PHB1 siRNA nanoparticles for cancer treatment Engineering
RNA interference (RNAi) represents a promising strategy for identification and validation of putative therapeutic targets and for treatment of a myriad of important human diseases including cancer. However, the effective systemic in vivo delivery of small interfering RNA (siRNA) to tumors remains a formidable challenge. Using a robust self-assembly strategy,...
Source: Proceedings of the National Academy of Sciences - June 23, 2015 Category: Science Authors: Zhu, X., Xu, Y., Solis, L. M., Tao, W., Wang, L., Behrens, C., Xu, X., Zhao, L., Liu, D., Wu, J., Zhang, N., Wistuba, I. I., Farokhzad, O. C., Zetter, B. R., Shi, J. Tags: Biological Sciences Source Type: research

Whole-genome siRNA screening for AAV permissivity Cell Biology
Viral vectors based on the adeno-associated virus (AAV) hold great promise for in vivo gene transfer; several unknowns, however, still limit the vectors’ broader and more efficient application. Here, we report the results of a high-throughput, whole-genome siRNA screening aimed at identifying cellular factors regulating AAV transduction. We identified 1,483...
Source: Proceedings of the National Academy of Sciences - September 8, 2015 Category: Science Authors: Mano, M., Ippodrino, R., Zentilin, L., Zacchigna, S., Giacca, M. Tags: Biological Sciences Source Type: research

Enhancing potency of siRNA for fusion genes Applied Biological Sciences
Canonical siRNA design algorithms have become remarkably effective at predicting favorable binding regions within a target mRNA, but in some cases (e.g., a fusion junction site) region choice is restricted. In these instances, alternative approaches are necessary to obtain a highly potent silencing molecule. Here we focus on strategies for...
Source: Proceedings of the National Academy of Sciences - December 1, 2015 Category: Science Authors: Gavrilov, K., Seo, Y.-E., Tietjen, G. T., Cui, J., Cheng, C. J., Saltzman, W. M. Tags: PNAS Plus Source Type: research

Correction for Yan et al., Suppression of NF-{kappa}B activity via nanoparticle-based siRNA delivery alters early cartilage responses to inȷury Correction
MEDICAL SCIENCES Correction for “Suppression of NF-κB activity via nanoparticle-based siRNA delivery alters early cartilage responses to injury,” by Huimin Yan, Xin Duan, Hua Pan, Nilsson Holguin, Muhammad Farooq Rai, Antonina Akk, Luke E. Springer, Samuel A. Wickline, Linda J. Sandell, and Christine T. N. Pham, which appeared in issue...
Source: Proceedings of the National Academy of Sciences - May 9, 2017 Category: Science Tags: Corrections Source Type: research

The effector mechanism of siRNA spherical nucleic acids Biochemistry
Spherical nucleic acids (SNAs) are nanostructures formed by chemically conjugating short linear strands of oligonucleotides to a nanoparticle template. When made with modified small interfering RNA (siRNA) duplexes, SNAs act as single-entity transfection and gene silencing agents and have been used as lead therapeutic constructs in several disease models. However,...
Source: Proceedings of the National Academy of Sciences - January 20, 2020 Category: Science Authors: Gokay Yamankurt, Robert J. Stawicki, Diana M. Posadas, Joseph Q. Nguyen, Richard W. Carthew, Chad A. Mirkin Tags: Physical Sciences Source Type: research

Cell-free reconstitution reveals the molecular mechanisms for the initiation of secondary siRNA biogenesis in plants Plant Biology
Secondary small interfering RNA (siRNA) production, triggered by primary small RNA targeting, is critical for proper development and antiviral defense in many organisms. RNA-dependent RNA polymerase (RDR) is a key factor in this pathway. However, how RDR specifically converts the targets of primary small RNAs into double-stranded RNA (dsRNA) intermediates...
Source: Proceedings of the National Academy of Sciences - July 30, 2021 Category: Science Authors: Yuriki Sakurai, Kyungmin Baeg, Andy Y. W. Lam, Keisuke Shoji, Yukihide Tomari, Hiro-oki Iwakawa Tags: Plant Biology Biological Sciences Source Type: research

Naringenin Produces Neuroprotection Against LPS-Induced Dopamine Neurotoxicity via the Inhibition of Microglial NLRP3 Inflammasome Activation
Conclusions: This study demonstrated that NAR targeted microglial NLRP3 inflammasome to protect DA neurons against LPS-induced neurotoxicity. These findings suggest NAR might hold a promising therapeutic potential for PD. Background Parkinson's disease (PD) is the second most prevalent central nervous system (CNS) degenerative disease. It is characterized by slow and progressive loss of dopamine (DA) neurons in the midbrain substantia nigra (SN) with the accumulation of α-synuclein in Lewy bodies and neuritis (1). Although the etiology of PD remains unclear, amounts of studies have suggested that ne...
Source: Frontiers in Immunology - April 30, 2019 Category: Allergy & Immunology Source Type: research

High-Throughput Characterization of Viral and Cellular Protein Expression Patterns During JC Polyomavirus Infection
Discussion The study of viral infections in vitro has provided innumerable advances to the field of virology. However, the lack of rapid and efficient screening tools has hindered research progress for some viruses, like JCPyV (Houff et al., 1983; Zu Rhein, 1983; Assetta and Atwood, 2017). To overcome this challenge, the development of high-throughput analyses is needed to help aid in the production of large data sets and generation of multiple lines of inquiry. Current methodologies for analyzing JCPyV infectivity predominantly rely on manual quantitation of infection by indirect immunodetection of viral proteins by epif...
Source: Frontiers in Microbiology - April 16, 2019 Category: Microbiology Source Type: research

Non-canonical Notch Signaling Regulates Actin Remodeling in Cell Migration by Activating PI3K/AKT/Cdc42 Pathway
In conclusion, our research results indicate that DAPT activates PI3K/AKT/Cdc42 signaling by non-canonical Notch pathway, and the activated Cdc42 promotes the filopodia formation and inhibits lamellipodia assembly, resulting in reduced migration of breast cancer cells. The results imply that non-canonical Notch signaling may play a very important role in the rapid response of cells to the extracellular signals. Author Contributions LG, JD, and LL designed the study and wrote and revised the manuscript. LL and LZ performed most of the experiments and data analysis. SZ, X-YZ, P-XM, Y-DM, Y-YW, YC, S-JT, and Y-JZ assisted i...
Source: Frontiers in Pharmacology - April 15, 2019 Category: Drugs & Pharmacology Source Type: research