Gene silencing nanocapsules: a new type of asthma treatment drug

A team of researchers from the University of Connecticut—including Jessica Rouge, assistant professor of chemistry at the College of Arts and Sciences, and associate professor of pathobiology at the College of Agricultural Health, worked with natural resources company Steven Szczepanek to develop novel asthma therapies using gene-silencing nanocapsules to help those who are unable to recover from the disease.

"When treating asthma, many people think that small-molecule anti-inflammatory drugs are feasible, but there are many asthma patients who do not respond to corticosteroids," Rouge said

Rouge's research team, including co-authors of 20 PhD students Shraddha Sawant and Alyssa Hartmann, designed nanomaterials and targeted therapies to deliver gene silencing messages to cells

Szczepanek explained that there are different types of asthma.

"When using nanomaterials, we try to implement treatments in a way that allows us to use fewer materials for greater results," Rouge said

Their system is based on the assembly of surfactants into micelles, similar to tiny bubbles, and occurs in a gradual process, resulting in the size of each micelle being around 60 nanometers

"First, we synthesize a surfactant, which is very similar to soap, essentially forming nano-sized bubbles

The nanocarbos were then characterized and tested in vitro whether they can cleave nucleic acid target cell lines.

"We proved that using our formula, these gene silencing sequences are effective, and we have seen them knock out the gene targets of interest

Rouge gave the data to Szczepanek to see his research team, including co-author and graduate student Tyler Gavitt’s 21 Ph.

As part of the postdoctoral research, Szczepanek conducted research on asthma, and his laboratory is equipped with equipment for the next step of research.

"I think this gene silencing technology is an excellent application for asthma treatment

The researchers tested the efficacy of GATA-3 DNAzyme-NAN in a mouse model of allergic asthma that is sensitive to house dust mites

"Not only did we see a dramatic reduction in the asthma phenotype in our mouse model, but we also tested GATA-3 DNAzyme-NANs in human leukocytes and found the uptake of nanoparticles and the down-regulation of gene expression of interest

Rouge pointed out another important detail: "Generally speaking, when you put nanoparticles into our lungs, you might think that they cause inflammation

Sawant said: "I believe that our unique nanostructure has great prospects in the field of oligonucleotide delivery

Rouge said that the next step is to obtain funding from NIH to continue this research: "We want to figure out where these nanocapsules have gone? We need to do a biodistribution study and other logical next steps, such as pharmacokinetics and determination.
How long do these treatments last in an organism
.
"

Researchers recently obtained a patent for the nanocapsule formulation, and they hope to commercialize it
.
Szczepanek explained that the team’s vision is that eventually, the technology can be delivered to patients via inhalers, just like current asthma medications, and depending on its exact formulation, it can target active inflammation or be used as a preventive measure.

.
Rouge added that this technology has the potential for customization
.

"The main theme is that, in general, different people respond differently to diseases, so it is possible to achieve personalized medicine
.
We are looking for a paradigm shift, because if you know someone’s genes, it’s In terms of intensity or overexpression, or if it is up-regulated, we can treat it, or at least suppress it
.
"

This research was funded by the University of Connecticut’s Accelerated Therapy Program for Healthcare (PATH) grant and the National Institutes of Health (NIH) grant R35GM138226-02
.

Journal Reference :

1. Tyler D.
   Gavitt, Alyssa K.
   Hartmann, Shraddha S.
   Sawant, Arlind B.
   Mara, Steven M.
   Szczepanek, Jessica L.
   Rouge.
   A GATA3 Targeting Nucleic Acid Nanocapsule for In Vivo Gene Regulation in Asthma .
   ACS Nano , 2021; 15 (7): 11192 DOI: 10.
   1021/acsnano.
   0c07781