Lipid nanoparticle mediated gene therapy: a new application for an established technology
Lipid nanoparticles are the most advanced non-viral gene delivery system and are enabling gene therapies on a large scale. They represent a new era of medicines where many genetic diseases can be cured (if not treated), and vaccines are produced within the body rather than by purification of non-infectious viruses. A lot of the development work on such nanoparticle systems stems from preliminary information gathered during the clinical translation of liposomes encapsulating small molecule drugs (see Doxil). Here we review in brief, the emergence of lipid nanoparticle formulations of nucleic acid from liposomal systems, and the differences in composition and manufacturing practices that have allowed for clinical translation.
In August 2018, the U.S. Food and Drug Administration approved the first therapeutic drug product based on a cellular process known as RNA interference (RNAi).
This formulation, named Patisiran (trade name Onpattro) was developed and is currently marketed by Alnylam. Onpattro is indicated for amyloidosis caused by mutations in the transthyretin gene; a fatal disease without treatments other than liver transplant. Results of the Phase III trial leading to the approval of Onpattro demonstrated that the formulation was able to reverse disease progression and increase quality of patients’ lives. The significance of this approval cannot be overstated – it ushered in a new era of medicines collectively known as non-viral gene therapies.
Onpattro delivers small nucleic acid fragments known as short interfering RNA (siRNA), and is reliant upon lipid nanoparticles (LNP) technologies to enable its functionality. siRNA interacts with proteins inside cells to promote the degradation of a specific messenger RNA (mRNA) molecule. Decreasing the amount of mRNA reduces the ability ...