Silencing of ADAM33 Expression by Using Antisense Oligonucleotides
Using ASO against ADAM 33 to reduce its expression and thus stopping airway remodeling in fibroblasts and muscle cells
Background
Asthma is a chronic respiratory disease that causes swelling of the airways due to inflammation and tightening of the muscles around the airways. It results in narrowing of the airways that carry air from the nose and mouth to the lungs. Structural changes of the airways associated with asthma are referred to as airway remodeling (cellular & extracellular matrix changes, apoptosis, muscle cell proliferation, fibroblast activation).
There is currently no cure for asthma, and treatment technologies depend on bronchodilators and steroids. ADAM33 has been discovered since early 2000s to play an essential role in asthma through airway remodeling however many attempts at targeting ADAM33 have failed.
Technology Overview
UMass Chan researchers have successfully created an ASO that targets ADAM33 in mice and are currently creating a humanized mouse model to test humanized ADAM33 sequences.
Stage of Development
- Invitro screen to identify murine sequences
- Invivo data indicating ADAM33 knockdown
- Invivo functional data in mouse asthma model
- Invitro identification of humanized sequence.
- Humanized mouse to be generated
- Humanized sequence to be tested in NHP lung tissue invitro •
Further Detail
- Locked Nucleic Acid Gapmers and Conjugates Potently Silence ADAM33, an Asthma-Associated Metalloprotease with Nuclear-Localized mRNA (2017)
- Unpublished data (in preparation)
Benefits
Targeting ADAM33 goes to the root cause of airway remodeling siRNA delivers very well to fibroblasts and muscle cells
Opportunity
- Licensing
- NewCo
- Part of a larger lung delivery platform