(71d) Zinc Finger Fusions: Attaching Protein to DNA for Drug Delivery and Sensing

A technique to bind protein to DNA in a site-specific manner without chemical modification would be a useful tool for drug or gene delivery and sensor applications. Attachment of a targeting domain to gene therapy vectors or siRNA can direct these compounds to specific cell types and enhance their therapeutic efficacy. Non-coding, nanostructured DNA scaffolds could be patterned with protein to serve as a new class of drug delivery vehicles or protein sensing arrays. Towards these ends we have developed a new method for attaching protein to DNA via zinc finger fusions. As proof of concept, a zinc finger (ZF) transcription factor with high affinity and specificity to an 18-base pair DNA sequence was expressed as a fusion to a lysozyme-binding, engineered 10th human type III fibronectin domain (Fn3). The bifunctional ZF-Fn3 fusion binds both to DNA and to lysozyme. This approach has synthetic flexibility and the potential to add any protein functionality to a DNA structure.