Adenoassociated viral vectors provide a safe and robust method for expression of transgenes in nondividing cells such as neurons. Intravenous injections of these vectors provide a means of transducing motoneurons of peripheral nerves. Previous research has demonstrated that serotypes 1, rh10 and PHP.B can transduce motor neuron cell bodies in the spinal cord, but has not quantified expression in the peripheral nerve axon. Axonal labeling is crucial for optogenetic stimulation and detection of action potentials in peripheral nerve. Therefore, in this study, serotypes 1, PHP.B, and rh10 were tested for their ability to label axons of the murine sciatic and tibial nerve following intravenous injection. Serotype rh10 elicits expression in 10% of acetylcholine transferase positive axons of the sciatic nerve in immunohistochemically-stained sections. Serotype rh10 transduces a variety of axon diameters from <1-12 μm, while PHP.B transduces larger axons of diameter (4-16 μm). Expression was not seen with serotype 1. These results show the potential of serotypes PHP.B and rh10 delivery of transgenic products to axons of the peripheral nerve.
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http://dx.doi.org/10.1016/j.neulet.2019.05.010 | DOI Listing |
J Bone Miner Res
January 2025
Human Genetics Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, United States.
We previously documented successful resolution of skeletal and dental disease in the infantile and late-onset murine models of hypophosphatasia (HPP), with a single injection of an adeno-associated serotype 8 vector encoding mineral-targeted TNAP (AAV8-TNAP-D10). Here, we conducted dosing studies in both HPP mouse models. A single escalating dose from 4x108 up to 4x1010 (vg/b) was intramuscularly injected into 4-day-old Alpl-/- mice (an infantile HPP model) and a single dose from 4x106 up to 4x109 (vg/b) was administered to 8-week-old AlplPrx1/Prx1 mice (a late-onset HPP model).
View Article and Find Full Text PDFJ Control Release
January 2025
Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, 430074 Wuhan, PR China; Shenzhen Key Laboratory of Viral Vectors for Biomedicine, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, 518055 Shenzhen, PR China; Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences, 430071 Wuhan, PR China; Key Laboratory of Quality Control Technology for Virus-Based Therapeutics, Guangdong Provincial Medical Products Administration, NMPA Key Laboratory for Research and Evaluation of Viral Vector Technology in Cell and Gene Therapy Medicinal Products, The Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, 518055 Shenzhen, PR China; University of Chinese Academy of Sciences, 100049 Beijing, PR China; Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, 200031 Shanghai, PR China. Electronic address:
The blood-brain barrier (BBB) is a formidable barrier that restricts the entry of substances into the brain, complicating the study of brain function and the treatment of neurological conditions. Traditional methods of delivering genes from the periphery to the central nervous system (CNS) using adeno-associated viruses (AAVs) often require high doses, which can trigger immune responses and hepatotoxicity. Here, we developed a new AAV variant named AAVhu.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Ophthalmology, Leiden University Medical Center (LUMC), Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
Viral vector delivery of gene therapy represents a promising approach for the treatment of numerous retinal diseases. Adeno-associated viral vectors (AAV) constitute the primary gene delivery platform; however, their limited cargo capacity restricts the delivery of several clinically relevant retinal genes. In this study, we explore the feasibility of employing high-capacity adenoviral vectors (HC-AdVs) as alternative delivery vehicles, which, with a capacity of up to 36 kb, can potentially accommodate all known retinal gene coding sequences.
View Article and Find Full Text PDFFood Environ Virol
January 2025
Wageningen Food Safety Research, Akkermaalsbos 2, 6708 WB, Wageningen, the Netherlands.
Viral contamination of bivalve molluscs, such as oysters, is a well-recognized food safety risk. The aim of this study was to assess virological hazards in market-ready oysters on the Dutch market. Non-targeted metagenome analysis was first performed on norovirus spiked-in samples showing linear and sensitive detection of norovirus GI.
View Article and Find Full Text PDFReprod Toxicol
January 2025
Department of Andrology, The First Affiliated Hospital, Hengyang Medical School, University of South China. Electronic address:
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