There is a growing need for monitoring or imaging gene therapy in the central nervous system (CNS). This can be achieved with a positron emission tomography (PET) reporter gene strategy. Here we report the development of a PET reporter gene system using the PKM2 gene with its associated radiotracer [F]DASA-23. The PKM2 reporter gene was delivered to the brains of mice by adeno-associated virus (AAV9) via stereotactic injection. Serial PET imaging was carried out over 8 wk to assess PKM2 expression. After 8 wk, the brains were excised for further mRNA and protein analysis. PET imaging at 8 wk post-AAV delivery showed an increase in [F]DASA-23 brain uptake in the transduced site of mice injected with the AAV mice over all controls. We believe PKM2 shows great promise as a PET reporter gene and to date is the only example that can be used in all areas of the CNS without breaking the blood-brain barrier, to monitor gene and cell therapy.
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http://dx.doi.org/10.1073/pnas.1901645116 | DOI Listing |
J Neuroinflammation
January 2025
Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA.
The thrombolytic protease tissue plasminogen activator (tPA) is expressed in the CNS, where it regulates diverse functions including neuronal plasticity, neuroinflammation, and blood-brain-barrier integrity. However, its role in different brain regions such as the substantia nigra (SN) is largely unexplored. In this study, we characterize tPA expression, activity, and localization in the SN using a combination of retrograde tracing and β-galactosidase tPA reporter mice.
View Article and Find Full Text PDFBMC Cancer
January 2025
Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan, 030001, China.
Background: Head and neck squamous cell carcinoma (HNSCC), a highly invasive malignancy with a poor prognosis, is one of the most common cancers globally. Circular RNAs (circRNAs) have become key regulators of human malignancies, but further studies are necessary to fully understand their functions and possible causes in HNSCC.
Methods: CircCCT2 expression levels in HNSCC tissues and cells were measured via qPCR.
Int J Biol Macromol
January 2025
Hebei Agricultural University, Baoding 071000, China. Electronic address:
WD40 superfamily genes are integral to various aspects of plant growth and development. Despite the economic importance and agricultural significance of the kiwifruit (Actinidia chinensis), a comprehensive characterization of the WD40 superfamily in this species remains elusive. In this study, we identified 280 WD40-encoding genes within the kiwifruit genome and systematically analyzed their phylogenetic relationships, gene structures, functional domains, and synteny.
View Article and Find Full Text PDFAppl Biochem Biotechnol
January 2025
Department of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital Affiliated to Tianjin Medical University, No.154 Heping Road to Anshan, Tianjin City, 300052, People's Republic of China.
Dysregulated circular RNAs (circRNAs) has been revealed to be involved in pulmonary fibrosis progression. Herein, this study focused on exploring the function and mechanism of circRNA Zinc Finger MYM-Type Containing 2 (circZMYM2) on idiopathic pulmonary fibrosis (IPF) using transforming growth factor (TGF)-β1-stimulated fibroblasts. Human fibroblast cell lines IMR-90 and HFL1 were stimulated with TGF-β1 to mimic fibrosis condition in vitro.
View Article and Find Full Text PDFPlant Cell Environ
January 2025
Department of Ecology & Evolutionary Biology, University of Toronto, Toronto, Ontario, Canada.
The C type of dicotyledonous plants exhibit a higher density of reticulate veins than the C type, with a nearly 1:1 ratio of mesophyll cells (MCs) to bundle sheath cells (BSCs). To understand how this C-type cell pattern is formed, we identified two SCARECROW (SCR) genes in C Flaveria bidentis, FbSCR1 and FbSCR2, that fully or partially complement the endodermal cell layer-defective phenotype of Arabidopsis scr mutant. We then created FbSCRs promoter β-glucuronidase reporter (GUS) lines of F.
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