Nasal spray gene therapy shows potential to treat lung diseases

Scientists at Mass General Brigham have unveiled a new viral delivery system designed to efficiently target the lungs and respiratory airways. The new adeno-associated virus variant, called AAV.CPP.16, can be administered through a nasal spray and has demonstrated remarkable efficacy in preclinical models. The findings, published in Cell Reports Medicine, offer hope for more effective treatments for respiratory diseases like pulmonary fibrosis and COVID-19.

A new frontier in gene delivery

The aim of gene therapy is to precisely deliver therapeutic genes to specific tissues in the body, a task typically assigned to adeno-associated viruses (AAVs). However, traditional AAV vectors have struggled to target the lungs effectively. Originally designed to penetrate the central nervous system, AAV.CPP.16 unexpectedly showed a strong ability to enter lung cells, inspiring researchers to explore its use in respiratory therapy.

“We noticed that AAV.CPP.16, which we initially engineered to enter the central nervous system, also efficiently targeted lung cells,” explained senior author Dr FengFeng Bei, of the Department of Neurosurgery at Brigham and Women’s Hospital. “This prompted us to further investigate AAV.CPP.16 for intranasal gene delivery to the respiratory airways.”

Superior performance in preclinical studies

AAV.CPP.16 was rigorously tested in various models, including cell cultures, mice and non-human primates. In all cases, it significantly outperformed previous AAV variants such as AAV6 and AAV9. Its success lies in its ability to effectively deliver genes directly to the lungs when administered intranasally, a non-invasive and patient-friendly approach.

Using this enhanced delivery method, the team successfully administered gene therapy in two key disease models. First, they targeted pulmonary fibrosis, a chronic lung condition characterised by scar tissue formation, by delivering genes that prevent scarring. Second, in a model of COVID-19, AAV.CPP.16 was used to deliver antiviral genes that inhibited the replication of SARS-CoV-2, the virus responsible for the disease.

Looking ahead

While the results are early and more research is needed before human trials can begin, the outlook is very promising. Intranasal delivery using AAV.CPP.16 could allow for safer, more effective gene therapies for a range of lung diseases.

“Although further research is needed, our findings suggest that intranasal AAV.CPP.16 has strong translational potential as a promising delivery tool for targeting the airway and lung,” said Bei.

As the research of gene therapy continues to develop, innovations like AAV.CPP.16 are taking us closer to targeted and less invasive treatments for complex respiratory conditions.