Journal
ACS NANO
Volume 15, Issue 7, Pages 11192-11201Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.0c07781
Keywords
DNAzyme; asthma; nanocarrier; GATA3; helper T cell
Categories
Funding
- University of Connecticut's Program in Accelerated Therapeutics for Healthcare (PATH) grant
- NIH [R35GM138226-02]
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The study demonstrates the use of peptide cross-linked nucleic acid nanocapsules for delivering GATA3-specific DNAzyme to immune cells to modulate transcriptional activity and behavior. The results show potential in decreasing the severity of asthma symptoms in both in vitro and in vivo models, warranting further investigation for clinical application.
Allergic asthma is one of the leading chronic lung diseases of both children and adults worldwide, resulting in significant morbidity and mortality in affected individuals. Many patients have severe asthma, which is refractory to treatment, illustrating the need for the development of new therapeutics for this disease. Herein, we describe the use of a peptide cross-linked nucleic acid nanocapsule (NAN) for the delivery of a GATA3-specific DNAzyme to immune cells, with demonstration of modulated transcriptional activity and behavior of those cells. The NAN, built from peptide cross-linked surfactants, is chemically designed to degrade under inflammation conditions releasing individual DNAzyme-surfactant conjugates in response to proteolytic enzymes. Using the NAN, GATA3 DNAzymes were delivered efficiently to human peripheral blood mononuclear cells, with clear evidence of uptake by CD4+ helper T cells without the need for harsh transfection agents. Knockdown of GATA3 was achieved in vitro using human Jurkat T cells, which express GATA3 under homeostatic conditions. Additionally, mice treated with DNAzyme-NANs during house dust mite (HDM)-induced asthma developed less severe allergic lung inflammation than HDM-only control mice, as measured by pulmonary eosinophilia. This study suggests that peptide cross-linked GATA3 DNAzyme-NANs may have the potential to decrease the severity of asthma symptoms in human patients, and development of this technology for human use warrants further investigation.
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