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Author (up) Li, S.; Jiang, Q.; Liu, S.; Zhang, Y.; Tian, Y.; Song, C.; Wang, J.; Zou, Y.; Anderson, G.J.; Han, J.-Y.; Chang, Y.; Liu, Y.; Zhang, C.; Chen, L.; Zhou, G.; Nie, G.; Yan, H.; Ding, B.; Zhao, Y. file  url
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  Title A DNA nanorobot functions as a cancer therapeutic in response to a molecular trigger in vivo Type Journal Article
  Year 2018 Publication Nature Biotechnology Abbreviated Journal Nat Biotechnol  
  Volume 36 Issue Pages 258264  
  Keywords Nanoscale; Robots; Drug delivery; Molecular trigger; Tumors; Cancer; Therapy  
  Abstract Nanoscale robots have potential as intelligent drug delivery systems that respond to molecular triggers. Using DNA origami we constructed an autonomous DNA robot programmed to transport payloads and present them specifically in tumors. Our nanorobot is functionalized on the outside with a DNA aptamer that binds nucleolin, a protein specifically expressed on tumor-associated endothelial cells, and the blood coagulation protease thrombin within its inner cavity. The nucleolin-targeting aptamer serves both as a targeting domain and as a molecular trigger for the mechanical opening of the DNA nanorobot. The thrombin inside is thus exposed and activates coagulation at the tumor site. Using tumor-bearing mouse models, we demonstrate that intravenously injected DNA nanorobots deliver thrombin specifically to tumor-associated blood vessels and induce intravascular thrombosis, resulting in tumor necrosis and inhibition of tumor growth. The nanorobot proved safe and immunologically inert in mice and Bama miniature pigs. Our data show that DNA nanorobots represent a promising strategy for precise drug delivery in cancer therapy.  
  Call Number Serial 2183  
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Author (up) Parsons, A.B.; Brost, R.L.; Ding, H.; Li, Z.; Zhang, C.; Sheikh, B.; Brown, G.W.; Kane, P.M.; Hughes, T.R.; Boone, C. file  url
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  Title Integration of chemical-genetic and genetic interaction data links bioactive compounds to cellular target pathways Type Journal Article
  Year 2004 Publication Nature Biotechnology Abbreviated Journal Nat Biotechnol  
  Volume 22 Issue 1 Pages 62-69  
  Keywords Biotechnology/*methods; Cluster Analysis; Drug Industry/*methods; *Drug Resistance; Fungal Proteins/metabolism; Gene Deletion; *Gene Expression Regulation; Mutation; Pharmacogenetics; Proton-Translocating ATPases/metabolism; Saccharomyces cerevisiae/*genetics; Software  
  Abstract Bioactive compounds can be valuable research tools and drug leads, but it is often difficult to identify their mechanism of action or cellular target. Here we investigate the potential for integration of chemical-genetic and genetic interaction data to reveal information about the pathways and targets of inhibitory compounds. Taking advantage of the existing complete set of yeast haploid deletion mutants, we generated drug-hypersensitivity (chemical-genetic) profiles for 12 compounds. In addition to a set of compound-specific interactions, the chemical-genetic profiles identified a large group of genes required for multidrug resistance. In particular, yeast mutants lacking a functional vacuolar H(+)-ATPase show multidrug sensitivity, a phenomenon that may be conserved in mammalian cells. By filtering chemical-genetic profiles for the multidrug-resistant genes and then clustering the compound-specific profiles with a compendium of large-scale genetic interaction profiles, we were able to identify target pathways or proteins. This method thus provides a powerful means for inferring mechanism of action.  
  Call Number Serial 339  
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