Researchers at Mass General Brigham have developed a novel nasal spray gene therapy using AAV.CPP.16, efficiently targeting lungs and airways. The therapy shows promise for treating respiratory diseases like pulmonary fibrosis and COVID-19, marking a major advancement in non-invasive gene delivery.
In a groundbreaking advancement in gene therapy, researchers from the U.S. have developed a novel method to deliver genetic treatments directly to the lungs and airway using a nasal spray. This innovation, spearheaded by scientists at Mass General Brigham, leverages a specially engineered version of adeno-associated virus (AAV) known as AAV.CPP.16, designed to enhance the efficiency of therapeutic delivery to respiratory tissues.
Gene therapy relies heavily on the ability to transport therapeutic molecules to the correct locations within the body. Traditionally, adeno-associated viruses have been used as delivery vehicles, but targeting specific areas like the lungs has remained a challenge—until now.
Originally engineered to penetrate the central nervous system, AAV.CPP.16 showed surprising effectiveness in targeting lung cells. “We noticed that AAV.CPP.16, which we initially engineered to enter the central nervous system, also efficiently targeted lung cells,” said FengFeng Bei, senior author of the study and a researcher in the Department of Neurosurgery at Brigham and Women’s Hospital.
This discovery led Bei and his team to explore the potential of intranasal delivery using the modified AAV vector. Their results, published in Cell Reports Medicine, showed that AAV.CPP.16 significantly outperformed older versions like AAV6 and AAV9 in delivering gene therapy in cell cultures, mouse models, and even non-human primates.
In practical applications, the team used AAV.CPP.16 to deliver gene therapy for pulmonary fibrosis, effectively preventing scarring in a mouse model of the disease. Additionally, the same approach was employed in combating SARS-CoV-2, the virus responsible for COVID-19. In this instance, the therapy successfully blocked viral replication in infected mice.
“Our findings highlight AAV.CPP.16 as a promising vector for respiratory and lung gene therapy,” the researchers concluded.
While more research is necessary before human trials, the team is optimistic about the future. “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,” Bei stated.
This nasal spray-based gene therapy method could mark a transformative step in treating chronic respiratory diseases and infections, offering a non-invasive, highly targeted, and efficient alternative to conventional therapies.
