RNA interference is a very attractive strategy for the treatment of human disease, however the therapeutic applicability of siRNAs has been hampered by the ineffective intracellular delivery of functional siRNAs to target cells in vivo. A focus of our laboratory is the design of LN systems that are able to effectively deliver their contents intracellularly following systemic administration, thus enabling the therapeutic use of siRNA. The challenge in this work is to develop LN systems that are stable when in the circulation but are able to destabilize biological membranes following arrival at target tissue.