[Nature-Biomedical Engineering]Gene delivery: Suddenly squeezed and shocked
Most studies in cell and molecular biology are carried out using tools and approaches that manipulate the extracellular microenvironment of cells. Only in a limited number of situations can the intracellular milieu of living cells be precisely perturbed and controlled. Typically, this is achieved by using molecular species that either passively or actively diffuse across the cell and nuclear membranes, or through active methods to load nanoparticles into cells, such as direct microinjection, the use of physical forces such as electroporation, and chemical means1. Yet intracellular-delivery methods are typically not high-throughput, do not consistently disrupt cells, cause significant cellular injury and death, and are not effective when delivering large or charged particles, such as DNA. Writing in Nature Biomedical Engineering, Klavs Jensen, Robert Langer and colleagues now describe the performance of an extremely high-throughput microfluidic approach involving mechanical and electrical breakdown of the plasma and nuclear membranes of cells to rapidly deliver DNA plasmids to the cell nucleus2.