Cell Reports Methods, Journal Year: 2024, Volume and Issue: 4(2), P. 100719 - 100719
Published: Feb. 1, 2024
In this issue of Cell Reports Methods, Parks et al. present an approach to non-invasively deliver adeno-associated viruses in a marmoset model using focused ultrasound (FUS) for neuronal tracing. The optimization technique non-human primate is highly valuable future FUS-mediated drug delivery studies.
Language: Английский
Advanced Drug Delivery Reviews, Journal Year: 2024, Volume and Issue: 211, P. 115363 - 115363
Published: June 19, 2024
Adeno-associated virus (AAV) vectors have emerged as a promising tool in the development of gene therapies for various neurological diseases, including Alzheimer's disease and Parkinson's disease. However, blood–brain barrier (BBB) poses significant challenge to successfully delivering AAV brain. Strategies that can overcome BBB improve delivery efficiency brain are essential successful brain-targeted therapy. This review provides an overview existing strategies employed brain, direct intraparenchymal injection, intra-cerebral spinal fluid intranasal delivery, intravenous injection BBB-permeable AAVs. Focused ultrasound has technology noninvasive spatially targeted administered by injection. also summarizes each strategy's current preclinical clinical applications treating diseases. Moreover, this includes detailed discussion recent advances emerging focused ultrasound-mediated delivery. Understanding state-of-the-art these approaches is critical future fulfill great promise treatment.
Language: Английский
Citations
10
Gene Therapy, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 1, 2025
Language: Английский
Citations
0
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown
Published: March 3, 2025
ABSTRACT Gene therapy for neurodegenerative diseases faces significant challenges due to the blood-brain barrier (BBB), which limits drug delivery central nervous system (CNS). While clinical trials Parkinson’s disease (PD) have progressed, administration of vectors expressing enzymatic or neurotrophic factor transgenes required extensive optimization method achieve potentially therapeutic levels transgene expression. Focused ultrasound (FUS) combined with microbubbles has emerged as a promising non-invasive strategy transiently open BBB targeted gene via viral nanocarriers including recombinant adeno-associated viruses (AAVs). However, key factors influencing FUS-mediated AAV delivery, dose distribution and efficacy, remain underexplored in non-human primates (NHPs). Here, we evaluated feasibility AAV9-CAG-GFP using two portable modalities: ultrasound-guided, spherically-focused FUS (USgFUS) novel low-frequency linear array configuration imaging called theranostic (ThUS). In mice, FUS-sonicated regions exhibited 25-fold increase AAV9 biodistribution compared systemic injection alone. Extending this approach NHPs, observed up 200-fold DNA treated brain regions, PD-relevant structures. assessing translational potential technique, ThUS-mediated AAV9-hSyn-hNTRN (human neurturin) toxin mouse model PD facilitated rescue 80% 75% degenerated dopaminergic neurons substantia nigra striatum, respectively. These findings demonstrate that technologies can non-invasively enhance both mice NHPs relative what be achieved intravenous (IV) same capsid With further development, these approaches may offer clinically viable, alternative diseases. One sentence summary opening increased after vector rhesus macaques.
Language: Английский
Citations
0
Cell Reports Methods, Journal Year: 2024, Volume and Issue: 4(2), P. 100719 - 100719
Published: Feb. 1, 2024
In this issue of Cell Reports Methods, Parks et al. present an approach to non-invasively deliver adeno-associated viruses in a marmoset model using focused ultrasound (FUS) for neuronal tracing. The optimization technique non-human primate is highly valuable future FUS-mediated drug delivery studies.
Language: Английский
Citations
1