Bacteriophage Host Range Engineering

Technology #16347

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Inventors
Professor Timothy Lu
Department of Electrical Engineering and Computer Science, MIT
External Link (www.rle.mit.edu)
Hiroki Ando
Department of Electrical Engineering and Computer Science, MIT
External Link (www.rle.mit.edu)
Sebastien Lemire
Department of Electrical Engineering and Computer Science, MIT
External Link (www.rle.mit.edu)
Managed By
Jon Gilbert
MIT Technology Licensing Officer
Patent Protection

Tuning Bacteriophage Host Range

US Patent Pending US 2015-0064770

Applications

This technology has applications in antibacterial therapies.

Problem Addressed

Overcoming the development of antibiotic resistance in pathogenic bacteria poses a tremendous medical challenge.   Whereas small molecule drugs have been the standard antibiotic for several decades, bacteriophages, or viruses that infect bacteria, could prove to be a viable alternative.  One significant challenge of bacteriophage-based therapy, is the specificity of each virus; thus, simultaneously targeting multiple bacteria in an infection would require a cocktail of viruses, complicating both development of therapies and increasing the associated regulatory hurdles.  One solution would be to engineer a single bacteriophage to target multiple hosts; however, current techniques for bacteriophage engineering are low in efficiency and throughput.

Technology

Researchers at MIT have developed a new method for addressing the challenges faced in engineering bacteriophage host ranges.  First, mutations are inserted into the tail region of phage DNA with PCR.  A library of mutated phage fragments is then transformed along with a yeast artificial chromosome (YAC) into a population of yeast, where homologous recombination between the phage fragments and the YAC can occur.  The resulting population of phage is extracted from the yeast, and then transfected into a bacterial colony, and tested for host range specificity.  Using this method allows for systematically generating and selecting phage variants with desired functionality.

Advantages

  • Systematically modify bacteriophage genome for wider range of specificities
  • Allows for modifying bacteriophage in non-bacterial host
  • Efficient and versatile method