Xandra Breakefield, PhD, on Trying New Approaches to AAV Therapy for Glioblastoma

"The thing I liked the best [about the research] was that it was really Lisa [Nieland’s] idea as a graduate student, she had me as a mentor who was a little [iffy about it] but she persisted and she was successful. I think this is about as exciting as it could be for a graduate student and teaches us all that we may have our preconceived notions about what is going to work and what isn't, but you don't know in science until you try.”

Glioma, and specifically glioblastoma, is an aggressive brain tumor with historically very poor outcomes, with a 1-year survival rate of 40% and a 2-year survival rate of 17%. The disease is a difficult one to treat, within the inherently challenging environment of the brain along with the blood brain barrier and potential neurotoxicity with targeted therapies.¹

Research out of the lab of Xandra Breakefield, PhD, investigator of neurology, Mass General Research Institute, and professor of neurology, Harvard Medical School, by Lisa Nieland, PhD candidate, was presented at the American Society of Gene & Cell Therapy (ASGCT) 27th Annual Meeting, held May 7 to 10, 2024, in Baltimore, Maryland, that investigated adeno-associated virus (AAV) delivery of Staphylococcus aureus Cas9 (saCas9) guided by a single-guide RNA to target microRNA-21 (miR-21) coding sequences in the genome in vivo. miR-21 is highly expressed in glioma cells responsible for tumor progression. The approach yielded reduced tumor growth and improved survival in mouse models.²

REFERENCES

1. Glioblastoma Multiforme. Webpage. 2024. American Association of Neurological Surgeons. https://www.aans.org/en/Patients/Neurosurgical-Conditions-and-Treatments/Glioblastoma-Multiforme 
2. Nieland L, Vrijmoet AB, Jetten IW, et al. All-in-One Adeno-Associated Virus Delivery for Therapeutic miR-21 Editing by saCas9 In Vivo. Presented at: ASGCT 27th Annual Meeting, May 7-10; Baltimore, Maryland. Abstract #113