A recent perspective article published in the journal Nature Reviews Drug Discovery discussed the evolution of lipid nanoparticles (LNPs) for nucleic acid delivery. The authors, Pieter Cullis, Professor of Biochemistry and Molecular Biology at the University of British Columbia, and Philip Felgner, Professor of Physiology and Biophysics at the University of California, Irvine, are co-inventors of lipid nanoparticle technology and pioneers in their use in gene therapy and vaccine delivery. Perspective: The 60-year evolution of lipid nanoparticles for nucleic acid delivery .
Image Credit: Kateryna Kon / Shutterstock Early studies on in vivo gene delivery showed that functional delivery can be achieved by injecting naked plasmids containing viral genomes cloned into eukaryotic expression vectors. However, the clinical utility of naked plasmid delivery strategies has been limited due to concerns about spontaneous DNA integration into the human genome and inefficient transfection. Besides, viral vectors for gene therapy were frequently associated with immune responses.
Most gene therapies currently in development use viral delivery systems, e.g., adeno-associated virus vectors.
Despite considerable progress, concerns regarding manufacturing, genetic capacity, and immunogenicity impede progress for viral vectors. The authors believe lipid-based delivery systems, such as LNPs, may become dominant due to their enhanced tolerability, safety, genetic capacity, ease of design, and manuf.