Gene Therapy and Immunology
Can the use of focused ultrasound to open the blood-brain barrier (BBB) help deliver gene therapy to the brain? Researchers are exploring this promising treatment for brain tumors and neurodegenerative diseases as they develop ways to circumvent both the BBB and the adhesive properties of the brain’s extracellular matrix.
In a study from the UK, focused ultrasound is being used to activate anti-tumor immune cells (lymphocytes) to slow tumor progression and prolong survival.
Central Nervous System Gene Therapy with Focused Ultrasound
Gene transfection in the brain: the Hanes/Price team from Johns Hopkins/UVA ed whether peripherally injected DNA-bearing, brain penetrating nanoparticles (DNA-BPN) could enter the brain after BBB opening with FUS to mediate localized, robust, and sustained transgenic expression in the rat brain. They found dose-dependent transgene expression in the FUS-treated region as early as 24 hours after administration, and the effect lasted for at least 28 days. In the treated region, approximately 42% of all cells, including neurons and astrocytes, were transfected as compared with less than 6% transfection in the contralateral (non-treated) hemisphere. Importantly, this was achieved without any sign of toxicity or astrocyte activation. The image-guided delivery of DNA-BPN with FUS and microbubbles thus constitutes a safe and non-invasive strategy for targeted gene therapy to the brain. See Targeted gene transfer to the brain via the delivery of brain-penetrating DNA nanoparticles with focused ultrasound published in the Journal of Controlled Release.
Adoptive cell transfer of focused ultrasound--activated cytotoxic T lymphocytes (CTLs) slows tumor growth and improves animal survival. Dr. Feng Wu and researchers at Oxford University are examining focused ultrasound—induced anti-tumor immunity, inhibition of tumor growth and progression, and survival benefit in tumor-bearing mice. Read Specific antitumour immunity of HIFU-activated cytotoxic T lymphocytes after adoptive transfusion in tumour-bearing mice published in the International Journal of Hyperthermia.