RT Journal Article
SR Electronic
T1 Nanoparticle-based thymulin gene therapy therapeutically reverses key pathology of experimental allergic asthma
JF Science Advances
JO Sci Adv
FD American Association for the Advancement of Science
SP eaay7973
DO 10.1126/sciadv.aay7973
VO 6
IS 24
A1 da Silva, Adriana L.
A1 de Oliveira, Gisele P.
A1 Kim, Namho
A1 Cruz, Fernanda F.
A1 Kitoko, Jamil Z.
A1 Blanco, Natalia G.
A1 Martini, Sabrina V.
A1 Hanes, Justin
A1 Rocco, Patricia R. M.
A1 Suk, Jung Soo
A1 Morales, Marcelo M.
YR 2020
UL http://advances.sciencemag.org/content/6/24/eaay7973.abstract
AB Despite long-standing efforts to enhance care for chronic asthma, symptomatic treatments remain the only option to manage this highly prevalent and debilitating disease. We demonstrate that key pathology of allergic asthma can be almost completely resolved in a therapeutic manner by inhaled gene therapy. After the disease was fully and stably established, we treated mice intratracheally with a single dose of thymulin-expressing plasmids delivered via nanoparticles engineered to have a unique ability to penetrate the airway mucus barrier. Twenty days after the treatment, we found that all key pathologic features found in the asthmatic lung, including chronic inflammation, pulmonary fibrosis, and mechanical dysregulation, were normalized. We conducted tissue- and cell-based analyses to confirm that the therapeutic intervention was mediated comprehensively by anti-inflammatory and antifibrotic effects of the therapy. We believe that our findings open a new avenue for clinical development of therapeutically effective gene therapy for chronic asthma.