2499-59-4Relevant articles and documents
Hydrophobic Nanoparticles Reduce the β-Sheet Content of SEVI Amyloid Fibrils and Inhibit SEVI-Enhanced HIV Infectivity
Sheik, Daniel A.,Chamberlain, Jeffrey M.,Brooks, Lauren,Clark, Melissa,Kim, Young Hun,Leriche, Geoffray,Kubiak, Clifford P.,Dewhurst, Stephen,Yang, Jerry
, p. 2596 - 2602 (2017)
Semen-derived enhancer of virus infection (SEVI) fibrils are naturally abundant amyloid aggregates found in semen that facilitate viral attachment and internalization of human immunodeficiency virus (HIV) in cells, thereby increasing the probability of infection. Mature SEVI fibrils are composed of aggregated peptides exhibiting high β-sheet secondary structural characteristics. Herein, we show that polymers containing hydrophobic side chains can interact with SEVI and reduce its β-sheet content by ～45% compared with the β-sheet content of SEVI in the presence of polymers with hydrophilic side chains, as estimated by polarization modulation-infrared reflectance absorption spectroscopy measurements. A nanoparticle (NP) formulation of this hydrophobic polymer reduced SEVI-mediated HIV infection in TMZ-bl cells by 60% compared with the control treatment. Although these NPs lacked specific amyloid-targeting groups, thus requiring high concentrations to observe biological activity, the use of hydrophobic interactions to alter the secondary structure of amyloids represents a useful approach to neutralizing the SEVI function. These results could, therefore, have general implications in the design of novel materials that can modify the activity of amyloids associated with a variety of other neurological and systemic diseases.
Non-Viral CRISPR/Cas Gene Editing In Vitro and In Vivo Enabled by Synthetic Nanoparticle Co-Delivery of Cas9 mRNA and sgRNA
Miller, Jason B.,Zhang, Shuyuan,Kos, Petra,Xiong, Hu,Zhou, Kejin,Perelman, Sofya S.,Zhu, Hao,Siegwart, Daniel J.
supporting information, p. 1059 - 1063 (2017/01/18)
CRISPR/Cas is a revolutionary gene editing technology with wide-ranging utility. The safe, non-viral delivery of CRISPR/Cas components would greatly improve future therapeutic utility. We report the synthesis and development of zwitterionic amino lipids (ZALs) that are uniquely able to (co)deliver long RNAs including Cas9 mRNA and sgRNAs. ZAL nanoparticle (ZNP) delivery of low sgRNA doses (15 nm) reduces protein expression by >90 % in cells. In contrast to transient therapies (such as RNAi), we show that ZNP delivery of sgRNA enables permanent DNA editing with an indefinitely sustained 95 % decrease in protein expression. ZNP delivery of mRNA results in high protein expression at low doses in vitro (?1). Intravenous co-delivery of Cas9 mRNA and sgLoxP induced expression of floxed tdTomato in the liver, kidneys, and lungs of engineered mice. ZNPs provide a chemical guide for rational design of long RNA carriers, and represent a promising step towards improving the safety and utility of gene editing.
PROCESS FOR PREPARING 4-HYDROXYBUTYL ACRYLATE
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Paragraph 0549; 0550; 0551; 0552; 0553; 0554; 0555; 0556, (2015/04/22)
A process for preparing 4-hydroxybutyl acrylate by transesterifying an alkyl acrylate with 1,4-butanediol in the presence of a dialkyltin oxide such that each of the alkyl groups has 4 to 8 carbon atoms, characterized in that the amount of the dialkyltin oxide is adjusted to 0.00001 to 0.01 moles per one mole of the alkyl acrylate.
