Columbia Technology Ventures

Bacterial genetic engineering system to treat infections

This technology is a CRISPR transposon-based system to generate genetic knockouts or introduce new functions in bacteria in situ.

Unmet Need: CRISPR technology with high efficiency for treatment of disease

Clustered regularly interspaced short palindromic repeats (CRISPR), along with a guide RNA and a Cas enzyme, is a technique that has been developed to target and alter DNA sites. Currently, the most common technology used is a CRISPR-Cas9 system that can cut and insert new sequences into DNA to alter a living organism’s genome. However, the integration efficiency of new insertions in this system is low. There is a need for a technology that increases the efficiency and integration of molecular cargo into the genome for suitable therapeutic development.

The Technology: Efficient bacterial genetic engineering system using CAST

This technology is a CRISPR-associated transposon (CAST) system that uses a conjugative vector with a CRISPR transposon and genetic payload to generate genetic knockouts or introductions in bacterial non-coding regions in situ. Genetic payloads can be expressed from the target’s genome for increased genomic stability in the form of nanobodies, binding proteins, enzymes, and other proteins of different types and sizes. This technology has been engineered to block virulence of Shiga toxin-producing bacteria. Compared to previous technologies, this CAST system is more efficient at inserting sequences and molecular cargo into the genome at multiple genomic sites. This technology can be adapted to generate many different genetic knockouts or introductions for other bacterial disease treatments.

This technology has been validated in mice infected with Shiga toxin-producing bacteria.

Applications:

  • Treatment for Shiga toxin-producing E. coli (STEC) infections
  • Treatment for other bacterial infections
  • Reprogramming of gut microbiome
  • Tool for screening antibiotic compounds
  • Tool for investigating mechanisms of bacterial interaction in biofilms

Advantages:

  • Increases insertion efficiency
  • Directs insertion of molecular cargo at multiple genomic sites
  • Adaptable
  • Expresses various types of protein

Lead Inventor:

Harris Wang, Ph.D.

Patent Information:

Patent Pending

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