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Potential gene therapy carriers created that mimic viruses, without the risk

Chemists 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.

The "nano" particle (a nanometer is roughly one-billionth of a yard) has the unlikely name of knedel (k-ned-l) because of its similarity to a popular Polish dumpling filled either with meat or sweets. The knedels are shell cross-linked structures surrounding a hydrophobic, or water insoluble, core domain. Needless to say, the knedels are too small to see with the naked eye. They have diameters ranging from 10 to 100 nanometers, so that they are of similar size to many globular proteins and viruses. In the body, they are expected to escape detection by the immune system.

Karen L. Wooley, Ph.D., professor of chemistry in Arts & Sciences, recently announced that she and her Washington University colleagues, Jianquan Liu, Ph.D., and Qi Zhang, Ph.D., both research assistants in chemistry, and Tomasz Kowaleski, Ph.D., research assistant professor in chemistry, have successfully hollowed out the knedel core to produce "nanocages" and attached a fluorescent tag to the core. They also attached a polypeptide called protein transduction domain (PTD) to the exterior of the nanostructure. They got this idea from Steven F. Dowdy, Ph.D., assistant professor of pathology at the Washington University School of Medicine in St. Louis. Dowdy demonstrated the efficiency with which PTD transduces proteins into cells.

With the aid of extremely powerful microscopes, Wooley and her colleagues were able to detect the peptide-bearing knedels binding to cell surfaces. Another group of nanoparticles without the PTD but with the fluorescent tags did not bind to target cells.

'New territory'

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 th
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Contact: Tony Fitzpatrick
tony_fitzpatrick@aismail.wustl.edu
314-935-5272
Washington University in St. Louis
2-May-2000


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