Synthesis of ligand-lipid conjugates to enhance intracellular delivery of siRNA-lipid nanoparticles to non-liver tissues in vivo
One of the most important biological advances made in the last 10 years has been the discovery of RNA interference (RNAi) and the ability of short pieces of RNA (siRNA) to inhibit protein synthesis with remarkable specificity and potency. This technology holds great promise as a new generation of highly active drugs with low side effects that can attack proteins that cause disease. However, siRNA molecules need to be inside cells to work, but are much too big to cross cell membranes in the way normal drugs can cross. AlCana has developed lipid nanoparticles (LNP) which carry siRNA molecules into cells using the same pathway used by some viruses to enter cells. The first generation of LNP get into liver cells very efficiently but to broaden their use as drugs we must develop LNP that can enter other cell types. This project aims to do this by making LNPs that can stick to the surface of non-liver cells and trigger the delivery of siRNA into those cells.