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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
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
Nanoparticles Deliver siRNA to Prevent Joint Damage, Hopefully Treat Osteoarthritis
As osteoarthritis wears away at joint cartilage, there are no available drugs to stop the process. Steroid injections help to reduce inflammation in the area, but they get washed away by the body in a short amount of time and the process continues. R...
Source: Medgadget - October 4, 2016 Category: Medical Equipment Authors: Editors Tags: Nanomedicine Source Type: blogs
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
Performance Assessment of Communicable Disease Surveillance in Disasters: A Systematic Review
Conclusion
Performance assessment is an integral component of the management of all organizations and the lack of performance assessment is considered a significant sign of weakness in an organization. Therefore, the lack of accepted mechanisms for the assessment of the performance of CDS systems in response to disasters is an important weakness. Although some studies attempted to assess surveillance systems, the results of this systematic literature review suggest that there is no clear and comprehensive assessment framework in place. While the CDC framework has been used in some studies, it is not specific for SS in resp...
Source: PLOS Currents Disasters - February 24, 2015 Category: Global & Universal Authors: javad 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
