دورية أكاديمية
أعرض في EDS

Microbubble drug conjugate and focused ultrasound blood brain barrier delivery of AAV-2 SIRT-3

التفاصيل البيبلوغرافية
العنوان: Microbubble drug conjugate and focused ultrasound blood brain barrier delivery of AAV-2 SIRT-3
المؤلفون: Dennison Trinh, Joanne Nash, David Goertz, Kullervo Hynynen, Sharshi Bulner, Umar Iqbal, James Keenan
المصدر: Drug Delivery, Vol 29, Iss 1, Pp 1176-1183 (2022)
بيانات النشر: Taylor & Francis Group, 2022.
سنة النشر: 2022
المجموعة: LCC:Therapeutics. Pharmacology
مصطلحات موضوعية: Focused ultrasound, microbubbles, BBB drug delivery, Sirtuin3, SIRT3, Parkinson’s, Therapeutics. Pharmacology, RM1-950
الوصف: Background Delivery of viral vectors as gene therapies to treat neurodegenerative diseases has been hampered by the inability to penetrate the blood brain barrier (BBB) and invasive or non-targeted delivery options prone to inducing immune responses. MR guided focused ultrasound (MR-g-FUS) and microbubbles have demonstrated safe, temporary, targeted BBB permeabilization clinically.Methods We developed clinically scalable, microbubble drug conjugates (MDCs) for the viral gene therapy, AAV.SIRT3-myc [adeno-associated virus expressing myc-tagged SIRT3], which has previously been shown to have disease modifying effects in animal models of Parkinson’s disease (PD). The lipid shells of the perfluorocarbon gas MDCs were covalently conjugated to antibodies with binding specificity to AAVs. Following systemic (iv) delivery of AAV.SIRT3-myc MDCs, MR-g-FUS was used to deliver SIRT3-myc to brain regions affected in PD. SIRT3-myc expression was determined post mortem, using immunohistochemistry.Results An in vitro, SH-SY5Y cell culture model was used to show that the localized destruction of MDCs using ultrasound exposures within biological safety limits dissociated AAV2-GFP (green fluorescent protein) from the MDCs in the targeted area while maintaining their transduction capacity. In rats, MR-g-FUS resulted in BBB permeabilization in the striatum and substantia nigra (SNc). SIRT3-myc was expressed in the striatum, but not the SNc.Conclusion These studies demonstrate that MDCs combined with MR-g-FUS are an effective method for delivery of viral vector gene therapies, such as AAV.SIRT3, to brain regions affected in PD. This technology may prove useful as a disease-modifying strategy in PD and other neurodegenerative disorders.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 10717544
1521-0464
1071-7544
Relation: https://doaj.org/toc/1071-7544; https://doaj.org/toc/1521-0464
DOI: 10.1080/10717544.2022.2035855
URL الوصول: https://doaj.org/article/829924003aa94284a5e1c9a07761be4d
رقم الأكسشن: edsdoj.829924003aa94284a5e1c9a07761be4d
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:10717544
15210464
DOI:10.1080/10717544.2022.2035855