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The research brief is a brief overview of interesting academic work.
The big idea
A new technique my colleagues and I have developed that can kill deadly, multidrug-resistant bacteria in real time could be used to generate targeted therapies that replace traditional, increasingly ineffective antibiotics.
Bacteria follow the same basic genetic process as all organisms: DNA, which contains instructions on how an organism looks and functions, is copied into an intermediate form called RNA which can be translated into proteins and the like. molecules that the body can use.
The technique we developed at the Chatterjee Lab at the University of Colorado at Boulder uses a synthetic version of RNA called PNA, or peptide nucleic acid, to disrupt this basic process in bacteria. Our PNA molecule clings to bacterial RNA, preventing it from doing its job. Because this molecule is a perfect match for bacterial RNA, it binds very tightly to RNA and resists degradation. This means that it can not only evade the bacteria’s error detection processes, but also prevent RNA from being translated into proteins and other useful biological molecules. This obstacle can be fatal for bacteria.
Our study, which we recently published in Communications Biology, demonstrates the therapeutic potential of a technique that can design, synthesize and test PNA treatments in less than a week.
Most antibiotics are not specific enough to target only infectious bacteria without destroying good bacteria in the body as well. Our technology, however, uses non-infectious versions of multidrug resistant bacteria to create highly specific molecules. By targeting only the pathogen of interest, these PNA therapies can prevent the damage that current antibiotics do to the good bacteria in the body.
Why is this important
The adaptation of bacteria to survive current antibiotics, or antibiotic resistance, is increasing.
The current therapeutic arsenal of medicine consists mainly of natural antibiotics which were isolated over 30 years ago. The discovery of new antibiotics in nature has stalled as bacteria continue to evolve and escape current treatments. And even if scientists discover a new natural antibiotic, research shows bacteria will start to develop resistance in as little as 10 years, leaving us in the same situation as before.
New types of therapies must be considered for a post-antibiotic era, a time when our arsenal of antibiotics is no longer effective. By using a system that can target specific bacteria and be continually modified based on emerging resistance patterns, doctors would no longer have to rely on chance findings. Treatments can adapt to bacteria.
What is not yet known
While we are exploring several characteristics that determine which RNA sequences are the best targets, more research is needed to identify the most effective PNA therapies against multidrug resistant bacteria. As our study only tested our new strategy on cell cultures in the lab, we will also need to see how it works in live animals to maximize the effectiveness of this type of treatment.
And after
Our team is currently testing the technology in different animal models against different types of infections. We are also exploring other PNA delivery options, including tailoring our bacterial delivery system to probiotic strains so that it can integrate with the healthy bacteria population that exists in the body.
With further development, our goal is to adapt the platform to target diseases that also use the same basic genetic processes as bacteria, such as viral infections or cancer.
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