Although it is only so-far described as proof of principle in an animal model of human disease, the potential versatility of the method will ensure a huge amount of further investment aimed at delivering practical treatments for many human infectious bacterial diseases.
As with all drugs, the issues are delivery, delivery, and delivery.
The method described relies on bacterial viruses to deliver a genetic drug and this may place some limitations on what can be achieved, but perhaps further innovation may open up several alternative ways of delivering this very highly targeted intervention.
A huge new advantage of the method is that it can be deliberately tailored to attack only pathogenic variants of bacteria. Resistant forms of the bacteria would in all likelihood have to evolve so as to have decreased virulence and harm potential so the drug is likely to mitigate the disease ability of infectious bacteria.
But virtually any well characterised bacterial disease can in principle be treated by the technique.
Supplied Summary:
Antibiotics target conserved bacterial cellular pathways or growth functions and therefore cannot selectively kill specific members of a complex microbial population. Here, we develop programmable, sequence-specific antimicrobials using the RNA-guided nuclease Cas9 (refs.1,2) delivered by a bacteriophage. We show that Cas9, reprogrammed to target virulence genes, kills virulent, but not avirulent, Staphylococcus aureus. Reprogramming the nuclease to target antibiotic resistance genes destroys staphylococcal plasmids that harbor antibiotic resistance genes3, 4 and immunizes avirulent staphylococci to prevent the spread of plasmid-borne resistance genes. We also show that CRISPR-Cas9 antimicrobials function in vivo to kill S. aureus in a mouse skin colonization model. This technology creates opportunities to manipulate complex bacterial populations in a sequence-specific manner.
@ Exploiting CRISPR-Cas nucleases to produce sequence-specific antimicrobials : Nature Biotechnology : Nature Publishing Group:
As with all drugs, the issues are delivery, delivery, and delivery.
The method described relies on bacterial viruses to deliver a genetic drug and this may place some limitations on what can be achieved, but perhaps further innovation may open up several alternative ways of delivering this very highly targeted intervention.
A huge new advantage of the method is that it can be deliberately tailored to attack only pathogenic variants of bacteria. Resistant forms of the bacteria would in all likelihood have to evolve so as to have decreased virulence and harm potential so the drug is likely to mitigate the disease ability of infectious bacteria.
But virtually any well characterised bacterial disease can in principle be treated by the technique.
Supplied Summary:
Antibiotics target conserved bacterial cellular pathways or growth functions and therefore cannot selectively kill specific members of a complex microbial population. Here, we develop programmable, sequence-specific antimicrobials using the RNA-guided nuclease Cas9 (refs.1,2) delivered by a bacteriophage. We show that Cas9, reprogrammed to target virulence genes, kills virulent, but not avirulent, Staphylococcus aureus. Reprogramming the nuclease to target antibiotic resistance genes destroys staphylococcal plasmids that harbor antibiotic resistance genes3, 4 and immunizes avirulent staphylococci to prevent the spread of plasmid-borne resistance genes. We also show that CRISPR-Cas9 antimicrobials function in vivo to kill S. aureus in a mouse skin colonization model. This technology creates opportunities to manipulate complex bacterial populations in a sequence-specific manner.
@ Exploiting CRISPR-Cas nucleases to produce sequence-specific antimicrobials : Nature Biotechnology : Nature Publishing Group:
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