Karen L. Wooley, Ph.D., professor of chemistry in Arts & Sciences, and colleagues at Washington University in St. Louis have created tiny synthetic polymer particles that mimic viruses and show potential for a new direction in gene therapy and other potential biomedical applications. Dubbed ‘knedels’ (an allusion to its similar appearance to a Polish food), the nanoparticles are shell cross-linked structures surrounding a hydrophobic (water insoluble) core domain. In the body, knedels are expected to escape detection by the immune system. By successfully hollowing out the knedel core to produce “nanocages,” to which a polypeptide called protein transduction domain (PTD) was attached. By monitoring the activity using fluorescent tags, the team demonstrated the efficiency with which PTD transduces proteins into cells. While the peptide-bearing knedels binding to cell surfaces, nanoparticles without the PTD did not bind to target cells. The accomplishment is a step toward using the knedel nanoparticles as potential gene therapy carriers, or vectors. Most gene therapy attempts today use live viruses that are weakened to carry RNA, DNA or other therapeutic payloads. However, gene therapy has met with great difficulties since its inception a decade ago, and much of the trouble surrounds the safe use of live viruses. Wooley’s knedels are biomimics – they are designed to behave like viruses, which biochemically are attracted to hosts that they seek to infect. A biomimic does not run the risk of a live virus. Beyond gene therapy, the team intends to explore the potential of the knedels as bio-scavengers. Because the particles also are chemically similar to lipoproteins, which comprise cholesterol, it might be possible to construct knedels that mimic high-density lipoproteins (HDL), so-called “good” cholesterol that scavenge low-density lipoproteins (LDL), or bad cholesterol.
SOURCE/REFERENCE: Washington University in St. Louis Press Release at http://news-info.wustl.edu
