Research Tools

The NIH Nanomedicine Program has supported the production of many research tools with potential uses beyond the Nanomedicine Development Centers’ goals.  Selected, published examples are listed below. 

Vectors/Constructs

• Genetic sensor for strong methylating compounds. (Moser et al., 2013).
• AAV variants that enable the selective targeting of genes to specific neurons, including in the retina of mouse (Caporale et al., 2011) and macaque (Dalkara et al., 2013).

Cell Cultures and Model Systems

• An optimized small molecule inhibitor cocktail for long-term maintenance of human embryonic stem cells, designed by using a feedback system control scheme (Tsutsui et al., 2011).

Structural Analyses

• Structural mechanistic analysis of TRiC inhibition of mhttQ51 aggregation by cryo-ET (Shahmoradian et al., 2013).
• Single-molecule super-resolution imaging and phenotype analysis of Htt-ex1 aggregates in PC12 cells (Sontag et al, 2013).
• Definitive TRiC subunit arrangement (Cong et al., 2010; Kalisman et al., 2012) and refined structures of open and closed states based on existing X-ray and cryo-EM data (Pereira et al., 2010).

Photoswitches

• The first light-gated native GPCRs and demonstration that they regulate synaptic function in brain slice and in vivo (Levitz et al., 2013).
• Red-shifted and spontaneously relaxing photoswitches (DENAQ, PhENAQ) (Mourot et al., 2011).
• One component system (AAQ) that can restore important aspects of vision to the blind mouse (Polosukhina et al., 2012).
• Channelrhodopsin-2 (ChR2) specific to parvalbumin-positive interneurons in the mouse primary visual cortex, used for optogenetic intervention in cortical neural activity (Lee et al., 2012).                                                         

Nanoparticles

• Bright and compact quantum dots with broadly tunable adsorption and fluorescence spectra (Smith and Nie, 2011).
• Protocells—porous nanoparticle-supported lipid bilayers for targeted delivery of multicomponent cargos to cancer cells (Ashley et al., 2011).
• Phi29 DNA-packaging motor for translocation of double-stranded DNA across membranes through nanopores (Wendell et al., 2009).

Computational Tools

• PROGNOS: An online bioinformatics tool predicts zinc finger and TALE nuclease off-target cleavage. 
  (Cradick et al., 2014; http://www.baolab.bme.gatech.edu/bao/Research/BioinformaticTools/prognos.html). 
• SAPTA: a new design tool for improving TALE nuclease activity.
  (Lin et al., 2014; http://baolab.bme.gatech.edu/Research/BioinformaticTools/TAL_targeter.html). 
• ROSIE—Rosetta Online Server that Includes Everyone 
  (Lyskov et al., 2013; http://rosie.rosettacommons.org).  
• MOTIF-EM: an automated computational tool for identifying conserved regions in CryoEM structures 
  (Saha et al., 2010; http://ai.stanford.edu/~mitul/motifEM/).