Dan Bonner

Health Sciences & Technology Grad Student
B.S. in Materials Science & Engineering, Cornell University
Hobbies: Running, playing/coaching basketball, cooking, eating
Hometown: Westborough, MA

Linear-Dendritic Block Copolymers for Targeted Gene Delivery

Nucleic acid therapies offer the promise to address unmet medical need in cancer, inherited genetic disorders, and vaccine development, but delivery of DNA to appropriate tissues is not yet clinically viable. DNA can be delivered via viral vectors with excellent efficiency, but this technique raises safety concerns and the possibility of immune rejection. Synthetic systems, generally polymer or lipid-based, have suffered from low transfection efficiency but are largely safe and biocompatible, though only transient gene expression is gained. Our lab has developed a modular, linear-dendritic block copolymer gene delivery system capable of transfecting a range of cell lines in vitro at efficiencies on par with standard commercially available non-viral vectors. Rather than taking gene expression as the sole endpoint of material performance, understanding relative efficiencies among various intracellular transport processes can shed light on important structure-property relationships. We have used an image-based, high throughput screening method for endosomal escape as well as more traditional confocal microscopy and flow cytometry methods to quantitate material performance with respect to intracellular barriers to gene delivery.

 Additionally, we are investigating the synthesis and characterization of next-generation block copolymer–DNA micelles which can disassemble in various cellular compartments depending on the chemical properties of the polymer. This is highly advantageous as DNA must be protected from degradation for as long as possible, but eventually must be released in order to be available for transcription. We are synthesizing a library of polymers with varied degradation properties and additional functional blocks. High-throughput analysis of the assembly, disassembly, uptake, endosomal escape, and gene transfer efficiency of the library enables structure-function relationships to be elucidated. Of particular mechanistic interest is the role played by unbound polymer during transfection, as the effective concentration can be drastically reduced in vivo due to serum binding.