RNA Switch Enables Drug-Controlled Gene Therapy Protein Production

In preclinical studies, researchers used the approach to activate production of a protein that helped reverse obesity and fat buildup in the liver (Source ID: 1). The adaptamer system works by using small-molecule drugs such as tetracycline or doxycycline to trigger a natural cellular process that allows cells to read genetic instructions and produce the desired protein. This offers a way to activate and reduce protein production without having to remove the gene therapy itself. [1]

To demonstrate the technology's therapeutic potential, the team engineered adaptamers to produce a protein called FGF21, which helps regulate metabolism and has shown promise for treating obesity (Source ID: 1). Preclinical studies showed that activating FGF21 production led to substantial weight loss, improved blood sugar regulation, and a near-complete reversal of fat buildup in the liver. However, excessive or prolonged exposure to FGF21 can contribute to muscle loss and reduced bone density, highlighting the importance of precise control. [1]

Bioengineers at the University of California San Diego have developed a technology that allows drugs to control when cells produce therapeutic proteins, which could potentially make gene therapies safer and more adaptable for treating chronic diseases (Source ID: 1). The technology uses adaptamers, which are short pieces of RNA that use small-molecule drugs to regulate protein production. This approach addresses a longstanding challenge in gene therapy: how to provide long-lasting treatment without allowing therapeutic proteins to remain active at potentially harmful levels (Source ID: 1). [1]

In preclinical studies, researchers used the approach to activate production of a protein that helped reverse obesity and fat buildup in the liver (Source ID: 1). The adaptamer system offers a way to activate protein production, as well as reduce it without having to remove the gene therapy itself. Drug exposure and concentration can influence how strongly the switch is activated. Meanwhile, removing the activating drug allows protein production to decline (Source ID: 1). [1]

To demonstrate the technology's therapeutic potential, the team engineered adaptamers to produce a protein called FGF21—which helps regulate metabolism and has shown promise for treating obesity—using a small-molecule drug such as tetracycline or doxycycline (Source ID: 1). Preclinical studies showed that activating FGF21 production led to substantial weight loss, improved blood sugar regulation and a near-complete reversal of fat buildup in the liver (Source ID: 1). [1]

The technology developed by bioengineers at the University of California San Diego allows drugs to control when cells produce therapeutic proteins, which could make gene therapies safer and more adaptable for treating chronic diseases (Source ID: 1). This approach addresses a significant challenge in gene therapy: the difficulty of controlling protein production after delivery of genetic instructions. Once those instructions are delivered, it can be difficult to manage how much protein cells produce and for how long (Source ID: 1). [1]

To achieve greater control, researchers in the lab of Prashant Mali developed what they call adaptamers—short pieces of RNA that use small-molecule drugs to regulate protein production (Source ID: 1). When a drug binds to an adaptamer, it activates a natural cellular process that allows cells to read genetic instructions and produce the desired protein. This system offers a way to activate protein production and reduce it without having to remove the gene therapy itself (Source ID: 1). [1]

Drug exposure and concentration can influence how strongly the switch is activated. Meanwhile, removing the activating drug allows protein production to decline. This raises the possibility of adjusting protein production through drug dosing, although further research is needed to establish how precisely protein levels can be controlled (Source ID: 1). [1]

Sources

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Prepared with AI assistance from the cited sources.