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Method for Installing Novel Functional Groups on Cells and Cellular Products

IB-1222

APPLICATIONS OF TECHNOLOGY:

  • Generation of novel cancer-selective therapeutics and diagnostic agents in vivo labeling
  • Selective drug targeting
  • Tissue engineering
  • ManLev reagent
  • Research:

              o studying retrograde transport

              o delivery of molecules to compartments of the secretory pathway

              o mapping biosynthetic pathways

              o diagnosis of certain pathogenic strains of bacteria

              o determining relative levels of glycosylation among cell types

              o neural cell patterning

ADVANTAGES:

  • Biosynthetic machinery for oligosaccharides less restrictive than other major biopolymers

  • Uses cell metabolism to incorporate functional groups on cell surface and in cell secretions.

ABSTRACT:

Berkeley Lab scientists have discovered a new method for incorporating novel functional groups onto cells and cellular products using the pathways for oligosaccharide biosynthesis. This technology is based on the discovery that unnatural reactive functional groups can be incorporated into cell surface-associated sialic acids. These groups can then be used as chemical "handles" for the attachment of biomolecules, or small molecular probes. This technique exploits the natural cell machinery, by synthesizing an unnatural biosynthetic precursor to sialic acid, which possesses a ketone group. This precursor is incorporated into cells metabolically, resulting in the cell-surface expression of ketone groups. The ketone is chemically unique to the cell surface and can be covalently ligated with hydrazide-conjugated proteins or small molecules under physiological conditions.

This technology revolutionizes the ability to interface biological tissue with synthetic substrates of defined molecular composition. New determinants for cell adhesion, immunological recognition or tissue targeting could be presented on ketone-coated cells by simply treating them with the hydrazine-conjugated biomolecules. For instance, ketone-coated cells could serve as selective targets for hydrazine-conjugated toxins, radionuclides or imaging reagents. This work also opens the possibility of designing mammalian cell bioreactors and artificial tissues.

This technology can be extended to other functional groups, other cell types, including bacteria and other microbes, and other monosaccharide biosynthetic pathways such as fucose.

STATUS:

To learn more about licensing a technology from LBNL see http://www.lbl.gov/Tech-Transfer/licensing/index.html.

REFERENCE NUMBER: IB-1222

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