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Tissue-Engineering Phage Therapy for Neural Regeneration

IB-2547

APPLICATIONS OF TECHNOLOGY:

  • Tissue engineering test
  • Therapy for spinal cord injuries
  • Information-mining tool for identifying peptide sequences
  • Potential for further medical and biotechnological applications

ADVANTAGES:

  • Virus-based materials create permissive and stimulating environment for neural cell regeneration
  • Synthetic substrate fosters orderly growth of neural fibers, helping directional guidance of neuronal cells in vivo
  • Long-rod shape of phage induces formation of highly organized liquid crystalline structures that affect cell polarization
  • Mass amplification easily realized using E. coli cells, produces large quantity of phage
  • Peptide-based signaling and therapeutic materials can simultaneously be displayed on phage coat proteins

ABSTRACT:

Seung-Wuk Lee and Anna Merzlyak of Lawrence Berkeley Laboratory have developed a genetically engineered M13 bacteriophage to produce a novel tissue-engineering material that can both support and influence cell growth and allow manipulation of cell behavior at the molecular level. This shows promise both for medical therapies and basic molecular biological research.

Due to its long filamentous shape and monodispersity, M13 bacteriophage (phage) can be engineered to self-assemble into directionally organized liquid crystalline structures that display a high density of cell-signaling peptides on their major coat proteins. This aligned nanofibrous system is capable of presenting a dense, periodic, single, or multifunctional peptide display. The constructed phage scaffolds can support neural progenitor cell proliferation and differentiation and control the orientation of their growth in three dimensions.

This provides many potential advantages over conventional tissue-engineering materials. Multiple signaling motifs can be easily displayed on viral surface protein coats in a controlled manner through genetic modification, and the single-stranded DNA of the phage provides therapeutic gene delivery tools. Identical basic building units can be easily prepared through bacterial amplification; three-dimensional, cell-containing scaffolds with long-range directional order can be easily produced via simple injection.

Evolutionary screening (phage display) can be used to identify previously unknown functional peptide motifs for expression on the viral coats, and mixing of the differently designed and engineered phage can be easily performed to present a controlled gradient of signaling motifs, allowing for investigation of individual as well as combined signals. Further investigation is needed to characterize immune responses to the engineered phage materials and to study the efficacy of the phage in tissue regeneration in vivo . Similar phage have been approved by FDA in 2006 and authorization of other applications of phage therapy should speed the approval process. Phage can be safely eliminated through the liver and lysosomal degradation.   

STATUS:

  • PCT publication WO/2009/120895 available at www.wipo.int. Available for licensing or collaborative research.

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

FOR MORE INFORMATION:

Merzylak, A., Indrakanti, S., Lee, S., "Genetically Engineered Nanofiber-Like Viruses For Tissue Regenerating Materials," Nano Lett., 13 January 2009. Available at http://pubs.acs.org

REFERENCE NUMBER: IB-2547

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Last updated: 07/08/2010