Tiny bubbles: Treating asthma with gene-silencing nanocapsules

(Nanowerk News) Steroid-based inhalers deliver life-saving medication for millions of asthma sufferers, providing relief and the ability to simply breathe. Unfortunately, inhalers do not work for all patients, and with rates on the rise for a disease that leads to hundreds of thousands of deaths world-wide each year, new asthma treatments and strategies are needed.
A team of UConn researchers – including Assistant Professor of Chemistry in the College of Liberal Arts and Sciences Jessica Rouge and Associate Professor of Pathobiology in the College of Agriculture, Health, and Natural Resources Steven Szczepanek – are collaborating to develop novel asthma therapeutics using gene-silencing nanocapsules in a bid to help patients who aren’t benefiting from existing treatments.
Their research was published in ACS Nano ("A GATA3 Targeting Nucleic Acid Nanocapsule for In Vivo Gene Regulation in Asthma").
“When treating asthma, many people think of small molecule anti-inflammatory medications as the way to go, but there are plenty of patients who have asthma who do not respond to corticosteroids,” says Rouge. “There’s an unmet need for creating different therapeutics that can suppress asthma for this group of people.”
Rouge’s research group, including co-authors Ph.D. student Shraddha Sawant and Alyssa Hartmann ’20 Ph.D., designs nanomaterials and targeted therapeutics that deliver gene silencing messages to cells. This paper details a nucleic acid nanocapsule (NAN) designed to selectively deliver an enzyme, called a DNAzyme, to silence a component of the immune response, called GATA-3, that leads to the over-expression of immune components that play a significant role in allergic asthma attacks.
Szczepanek explains there are different types of asthma, and this technology is designed to treat allergic asthma specifically, which constitutes about 50% of cases in adults and 90% in children. GATA-3-based treatments are already showing promise in clinical trials, and Rouge says that by pairing the sequence with nanotechnology, they hope to provide more efficient means of delivery and treatment straight to the source of inflammation.
“When using nanomaterials, we try to administer the therapy in a way that could allow us to use less materials to get a bigger effect,” Rouge says.
Their system is based on surfactants that assemble into micelles, similar to tiny bubbles, and occurs in a stepwise process, resulting in each being around 60 nanometers in size.
“First, we synthesize something called a surfactant, it’s much like soap and essentially forms a nanoscale bubble. Then we modify the surface chemistry of this bubble so it can conjugate or connect to DNA. The next step, and what’s unique to our lab, is we use enzymes to build the next piece to attach the DNA sequence that essentially cleaves mRNA encoding GATA-3,” Rouge says.
The nanocaspules were then characterized and checked if they could cleave the nucleic acid target cell lines in vitro and the results were promising.
Source: University of Connecticut
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