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Evasion of restriction-modification barriers for bacterial genetic engineering

Methods to allow the expression of small plasmid “minicircles” in virtually any bacterial strain, even those previously described as genetically intractable

  • Stage: Preclinical in vitro
  • Type: Diagnostic
  • Categories: Microbiome

Technology Overview

Many common strains of bacteria are difficult to genetically manipulate due to endogenous defense mechanisms called restriction-modification (RM) systems which utilize endonucleases to degrade foreign DNA. These RM systems thus impede our ability to study many different types of disease-causing bacteria, as well as limit the development of bacterial species for commercial use. Current methods to overcome these RM systems are expensive, inefficient, and aren’t well applied across different bacterial strains. The Johnston lab has developed a method to produce species-specific minicircle plasmids lacking certain RM endonuclease motifs which effectively “blind” bacterium to foreign DNA during artificial transformations. Termed “SyngenicDNA”, this method has been validated in proof-of-concept experiments with clinically relevant Staphylococcus aureus bacteria and enables efficient and flexible genetic manipulation in previously intractable species.

Applications

  • Efficient genetic manipulation of disease-causing bacterial species
  • Enables the expanded use bacteria within industrial processes such as biofuel production
  • Allows commercial development of different probiotic bacterial species

Advantages

  • Less expensive and more efficient than current approaches to overcome RM systems
  • Allows genetic access to previously intractable species

Patent Information

WO2018071841, other IP pending

Market Overview

The market for clinical microbiology is predicted to reach $4.95 billion USD by 2023 growing at a CAGR of 6.4%, while the global biofuel market was valued at $168 billion USD in 2016 and is expected to reach 218.7 billion USD in 2022. The global probiotics market size is expected to expand from $ 43.38 billion USD at a CAGR of 6.9 percent between 2018-2022.

Investigator Overview

  • Chris Johnston, PhD, Vaccine and Infectious Disease Division
Tech ID: 19-146
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