(205d) A Lipid Nanoparticle siRNA Delivery System for B Cell Lymphoma

Each year, Non-Hodgkin lymphoma kills over 20,000 people in the United States, and an additional 70,000 individuals are diagnosed with the disease. Historically, lymphoma has responded quite positively to the addition of new therapies to multi-drug regimens. Therefore, siRNA therapy, which could silence the expression of oncogenes, has the potential to enhance the potency of current treatments. Unfortunately, B cells are notoriously difficult to transfect with siRNA, and the primary obstacle to the development of RNAi lymphoma therapy has been the lack of potent delivery systems. To address this challenge, we have developed lipid-like nanoparticles that effectively encapsulate siRNA and deliver it into both Eu-myc Burkitt’s lymphoma cells and JeKo-1 Mantle Cell lymphoma cells. These nanoparticles facilitate up to 90% silencing at the mRNA level in lymphoma cells at a dose as low as 10 nM. Furthermore, lipid nanoparticles can be decorated with ligands specific against CD22, a B cell surface receptor that promotes cellular internalization upon binding. CD22 ligands mediate over two orders of magnitude better binding to lymphoma cells that to other immune cells (e.g. RAW 264.7 macrophages). Together, these data indicate that lipid nanoparticles have potential as siRNA delivery vehicles for the targeted treatment of Non-Hodgkin B cell lymphoma as well as its genetic study.