RNA interference (RNAi) is a very attractive strategy for the treatment of human disease, however the therapeutic applicability of small-interfering RNAs (siRNAs) has been hampered by the inability to delivery siRNA to the disease site and the ineffective intracellular delivery of functional siRNAs to target cells in vivo. A focus of our laboratory is the design of LNP 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 potent LNP systems that are well tolerated, able to evade the immune system and remain stable in the circulation.
Delivery of Plasmid DNA
Many diseases such as cancer, cystic fibrosis and sickle cell anemia are caused by mutations in genes resulting in nonfunctional protein. Gene therapy using plasmid DNA has the potential of restoring these functions by re-introducing essential genes into the cell. This however has been largely unsuccessful and have proven problematic due to the potential risk of random disruption of the genome by viral carriers and the potential for immune stimulation. A focus in our lab is to develop and optimize LNPs to deliver plasmid DNA safely and effectively in vitro and in vivo as an alternative to viral delivery for gene therapy.
Delivery of Other Nucleic Acids
Because all nucleic acids (DNA and RNA) share similar properties and by applying our knowledge of LNP systems for the delivery of siRNA and plasmid DNA, our lab has recently been exploring the delivery of messenger RNA (mRNA) for gene therapy or microRNA (miRNA) for gene silencing and regulation.