CLL-targeting DNA Origami drug delivery
OhioMod is a group of undergraduate students participating in BioMod, an international design competition at Harvard University. The intent of the competition is to provide students with an opportunity to engineer nanoscale biomolecular objects for therapeutic or scientific endeavors. This year, twenty-nine students from ten different countries convene in Harvard on November 1st for their third annual jamboree. Each undergraduate team is expected to produce both a video and website highlighting their research over the summer. As the team representing The Ohio State University we are searching for sponsors to help fund our trip to Harvard this autumn. Our goal for the competition is to use self-assembed DNA nanostructures to target chronic lymphocytic leukemia with intercalating drugs.
The backbone of our project is based on using the novel technique of DNA origami in which we use computer-aided software to design DNA that will fold itself into a desired shape. Dr. Carlos Castro has greatly developed this protocol and will be guiding us for this portion of the project. The folded DNA structure can then be loaded with intercalating drugs such as Daunorubicin or Doxorubicin and then be delivered to the target cell group. This drug delivery is inspired from Qiao Jiang’s paper DNA Origami as a Carrier for Circumvention of Drug Resistance in which Doxorubicin attached to DNA origami presented remarkable cell-killing activity to Doxorubicin-resistant cancer cells. We will be focusing our drug delivery on CLL cells due to the already existing collaboration existing between Dr. Chris Lucas of our lab and Dr. John Byrd of the CLL experimental therapeutics group at the Comprehensive Cancer Center at The Ohio State University Wexner Medical Center.
Once we have determined the loading efficiency of various DNA structures, we will then conjugate antibodies directed against known antigens of CLL including CD37, CD20, and ROR1. We find that CD37 to be a strong candidate due to the already existing CD37-SMIP that was engineered in one of Dr. Byrd’s groups, as well as ROR1 for its selectivity and relatively recent foray into mAb therapy. An application with attaching antibodies to the DNA origami is already being explored by Dr. Chris Lucas. The structures will then be introduced to CLL cells including MEC1 and locally derived OSUCLL cell lines.
We believe we will be successful in the competition due to well-established current methods available to us in DNA origami assembly in Dr. Castro’s lab allowing us to quickly engineer nanostructures, as well as the potential for collaboration with the many groups targeting CLL at OSU. Leukemia itself is expected to be an effective in vivo cancer target due to the smaller amount of physiological barriers in the bloodstream that the DNA origami would have to overcome. Also, DNA origami itself as a drug agent is advantageous because of the little to none immunogenic response to DNA, and as a natural carrier of intercalating drugs.
We therefore look forward to any future collaboration from your group, as well as for any sponsorship that would help fund our trip to Harvard. Your time is much appreciated.