Towards the targeted phage-based nanodelivery of genome editing complexes to render pathogenic skin bacteria harmless

Grantee: Associate Professor Nicholas Taylor, Faculty of Health and Medical Sciences, University of Copenhagen

Amount: DKK 2,996,539

Bacterial skin infections are caused by bacteria that rely on several proteins to be infectious and resist antibiotic treatment. These proteins are encoded in the genome, or DNA, of the bacteria.

The specific knockout of these genes by genome editing has been shown to inhibit pathogenic bacteria, but delivery of the complexes that perform these modifications is still a major challenge.

To overcome this hurdle, we propose to use the large protein-injecting bacteriophage (a virus that can infect a bacterium) to inject a genome editing complex into bacteria. We will investigate the structure of the bacteriophage, to better understand which parts we can modify. We will exchange the recognition target of the bacteriophage, so that it can specifically bind to a bacterium of choice.

Additionally, we will modify the large protein of the bacteriophage that it normally injects, and replace it with a genome-editing complex: this will allow the targeted destruction of the DNA fragments in the bacterium that encode a protein that allows it to survive antibiotic treatment.

Our results will pave the way for the targeted delivery of genome editors to dangerous skin bacteria to make them harmless and more susceptible to antibiotic treatment.