I have identified ways to transfect DCs efficiently (in vitro) with mRNA nanoparticles without excessive toxicity. By using an optimal gene carrier, mRNA constructs, optimized nanoparticle properties, and targeting non-degradative endocytic pathways of DCs as well as manipulating translation of exogeneously delivered 5’ capped mRNA molecules, primary murine DCs, DC cell lines (JAWS II and DC2.4) and primary human DCs can be efficiently transfected. We are currently optimizing the formulation for in vivo applications, with emphasis on exploiting the advantages of a particle approach to mRNA immunotherapy – such as coencapsulation of antigen/adjuvant molecules and targeted delivery to DCs.
Publications:
Microscale oral delivery devices incorporating nanoparticles. Phua K, Leong KW. Nanomedicine (Lond). 2010 Feb;5(2):161-3.
Degradable Polymers. Phua K.K.L., Roberts E.R.H., and Leong K.W. Comprehensive Biomaterials. 2011. vol. 1, pp. 381-415 Elsevier.
