The Adaptosome, a Nanoscale Delivery System for Specific Cell Targeting

Roy Ogle

Departments of Medicine, Biomedical Engineering, UVa

Anthony Spano

Department of Biology, UVa

The targeted delivery of drugs or nucleic acids to specific cells such as stem cells or cancer cells remains a central obstacle to basic research and the successful application of gene therapy. The ultimate goal of this project is to construct and test the efficacy of a protein-based self-assembling nanoparticle we term an “adaptosome”, a nanometer-sized delivery system that can be used for specific cell targeting. We propose to first utilize an in vitro self-assembling gene transfer agent (GTA) prohead system to encapsidate nucleic acids (siRNA and/or antisense DNA (1). We will then modify the loaded prohead using peptides designed to mediate specific attachment and uptake into target cells. System specificity will be provided by modular, bi-functional dipeptide adapter molecules (adaptomers), one end of which will bind the prohead, while the opposite end provides a peptide for targeting and transport across the cell membrane. Finally, as proof or principle, we will test the function of the particles by following the adaptosome-mediated uptake of siRNA and/or antisense DNA into rat adipose stem cells (ASCs), measuring the ability of the delivered nucleic acid to reduce the level of expression of a target gene, enhanced green fluorescent protein (EGFP) overtime. The successful completion of this work will provide a first step towards providing biomedical researchers with a cheap, versatile, easily constructed vehicle fro directing drugs to their site of action in vitro or in vivo.