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Gene-silencing nanocapsules could treat asthma

16 August 2021
Appeared in BioNews 1108

A new treatment that uses nanocapsules to silence a gene responsible for allergic asthmatic reactions has been developed by scientists.

Asthma is a condition that affects a person's breathing capacity in response to an external stimulus. The most common asthma treatment is corticosteroids dispensed through inhalers; however, it is believed that up to ten percent of asthmatics do not respond to this form of therapy. Now, researchers from the University of Connecticut have developed nanocapsules that travel to the body's immune cells, whereupon they degrade in the presence of a transcriptional regulator responsible for the inflammatory response in asthmatics, and release a DNAzyme, which inhibits the allergic immune response.

'There's an unmet need for creating different therapeutics that can suppress asthma for this group of people' said Dr Jessica Rouge, who led the study. 

Ninety percent of adult asthmatics have atopic asthma, which means their symptoms are the result of an allergic response. Atopic asthma causes the inflammation and narrowing of their airways as well as the over secretion of mucus from the airway's lining. This is part of an immune response to substances they are allergic to such as house dust mites, and is regulated by the transcription factor GATA3.

The study, published in the journal ACS Nano, found that mice prone to allergic asthmatic attacks from dust mites, registered lower autoimmune responses and inflammation in their lungs and respiratory tract when treated with the nanocapsules containing DNAzymes designed to reduce expression of GATA3, in comparison to a control group. Lower expression of the GATA3 gene in the lung tissue of the mice treated with the nanoparticles was also found. 

A similar response was also seen in both the GATA3 gene expression and nanocapsule uptake when human white blood cells were exposed to the nanocapsules. 

The group felt that these results further endorsed the suitability of these nanocapsules for use in treating humans with asthma.

'I am happy to be a part of this collaborative research as it marks the beginning of the development of the [nanocapsule] as an effective in vivo nanocarrier' said Shraddha Sawant, a PhD student in Dr Rouge's research group. 

Some concerns were expressed by the researchers around the ingestion of nanoparticles triggering inflammatory autoimmune responses. 'Generally speaking, when putting nanoparticles in our lungs, you might think they could cause inflammation. However, we were really excited that at doses we used, the nanocarrier alone didn't cause inflammation' said Dr Rouge.

The nanocapsule design has recently been patented by the research group and they are hoping to secure more funding in order to further characterise their in vivo behaviour as well as how long they last within the body. 

A GATA3 targeting nucleic acid nanocapsule for in vivo gene regulation in asthma
ACS Nano |  23 June 2021
Tiny bubbles: treating asthma with gene silencing nanocapsules
University of Connecticut Today |  11 August 2021
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