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Potential Gene Therapy Carriers Created That Mimic Viruses, Without The Risk

Date:
May 3, 2000
Source:
Washington University In St. Louis
Summary:
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.

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.

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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 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. The difficulty reached tragic proportions in September 1999, when an 18-year-old gene therapy patient died after being injected with a genetically altered adenovirus carrying a gene to control the boy's enzyme deficiency.

Wooley's knedels are biomimics - they are designed to behave like viruses, which biochemically are attracted to hosts that they seek to infect. But a biomimic does not run the risk of a live virus, which, as in the case of the 18-year-old who died, may have toxic or, on the other hand, negligible effects.

"We're combining synthetic constructs with biological pieces," explains Wooley. "It's what is called bioconjugation, and it's really a whole new territory for us. We're interested in making nanoparticles with the hollow cages into which one could put peptides, genes, proteins and small molecule drugs, all sorts of biomedical possibilities, even scavenging other cells or molecules. Other researchers are doing similar things in particle research, but they can't seem to get down to the same size range that we can."

Wooley presented the details of these latest results at the American Chemical Society's National Meeting, held March 26-31, 2000, in San Francisco.

Beyond gene therapy, Wooley and her group intend 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.

Next up for Wooley is a search for the appropriate genetic material to place into the nanocage for delivery to host targets.

"We don't have a candidate yet, but we're confident we will find one," Wooley says. "We've come a long way with knedels, with still farther to go."


Story Source:

The above story is based on materials provided by Washington University In St. Louis. Note: Materials may be edited for content and length.


Cite This Page:

Washington University In St. Louis. "Potential Gene Therapy Carriers Created That Mimic Viruses, Without The Risk." ScienceDaily. ScienceDaily, 3 May 2000. <www.sciencedaily.com/releases/2000/05/000502190235.htm>.
Washington University In St. Louis. (2000, May 3). Potential Gene Therapy Carriers Created That Mimic Viruses, Without The Risk. ScienceDaily. Retrieved November 26, 2014 from www.sciencedaily.com/releases/2000/05/000502190235.htm
Washington University In St. Louis. "Potential Gene Therapy Carriers Created That Mimic Viruses, Without The Risk." ScienceDaily. www.sciencedaily.com/releases/2000/05/000502190235.htm (accessed November 26, 2014).

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