AI Article Synopsis
- The study investigates the efficiency of different recombinant adeno-associated virus (rAAV) serotypes for delivering genes to joints in rheumatoid arthritis treatment.
- It specifically compares rAAV-2/1, rAAV-2/2, and rAAV-2/5 as means to deliver genes encoding murine secreted alkaline phosphatase (mSEAP) and Escherichia coli beta-galactosidase.
- Results indicate that the rAAV-2/5 serotype demonstrates significantly higher transgene expression in mouse models, lasting over 130 days, which suggests promising implications for gene therapy in RA.
Article Abstract
The potential for gene delivery to joints, using recombinant adeno-associated virus (rAAV) vectors for the treatment of rheumatoid arthritis (RA), has received much attention. Different serotypes have different virion shell proteins and, as a consequence, vary in their tropism for diverse tissues. The aim of this study was to compare the transduction efficiency of different AAV serotypes encoding murine secreted alkaline phosphatase (mSEAP) or Escherichia coli beta-galactosidase for intraarticular gene delivery in an experimental model of arthritis. The vectors contained AAV2 terminal repeats flanking the reporter gene in an AAV1, AAV2, or AAV5 capsid, producing the pseudotypes rAAV-2/1, rAAV-2/2, and rAAV-2/5. Left knee joints of mice with collagen-induced arthritis were injected and transgene expression was analyzed by chemiluminescence or direct in situ staining of frozen sections. We show for the first time that intraarticular gene transfer with AAV- 2/5 was far more efficient than with the other serotypes tested. Transgene expression was detectable as early as 7 days after injection, reached a maximum at 21 days, and was stably expressed for at least 130 days, whereas AAV-2/1- and AAV-2/2-mediated expression levels were barely detectable. These findings provide a practical application for future local AAV-mediated gene therapy trials in RA.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1089/hum.2005.16.426 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Mesencephalic astrocyte-derived neurotrophic factor inhibits neuroinflammation through autophagy-mediated α-synuclein degradation.
Arch Gerontol Geriatr
December 2024
Department of Neurology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, China. Electronic address:
Article Synopsis
- Parkinson's disease (PD) is characterized by the loss of dopamine neurons and is influenced by α-synuclein aggregation and neuroinflammation, with microglia playing a key role.
- Previous research identified mesencephalic astrocyte-derived neurotrophic factor (MANF) as a potential inhibitor of α-synuclein accumulation and neuroinflammation, though its molecular mechanisms were not fully understood.
- This study found that reducing MANF expression increased inflammation (TNF-α), while exogenous MANF promoted autophagy, reduced α-synuclein levels, and inhibited neuroinflammation, suggesting that MANF could be a therapeutic target for PD through its role in autophagy.
Production of Recombinant Adeno-Associated Virus Through High-Cell-Density Transfection of HEK293 Cells Based on Fed-Perfusion Culture.
Hum Gene Ther
January 2025
School of Bioengineering, East China University of Science and Technology, Shanghai, China.
Adeno-associated virus (AAV)-associated gene therapy has been increasingly promising, in light of the drugs progressed to clinical trials or approved for medications internationally. Therefore, scalable and efficient production of recombinant AAV is pivotal for advancing gene therapy. Traditional methods, such as the triple-plasmid transfection of human embryonic kidney 293 cells in suspension culture, have been widely employed but often hampered by low unit yield.
View Article and Find Full Text PDFALG5 downregulation inhibits osteogenesis and promotes adipogenesis by regulating the N-glycosylation of SLC6A9 in osteoporosis.
Cell Mol Life Sci
January 2025
Department of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-sen University, No. 3025, Shennan Middle Road, Futian District, Shenzhen, 518033, Guangdong, China.
Osteoporosis is characterized by decreased bone mass and accumulation of adipocytes in the bone marrow. The mechanism underlying the imbalance between osteoblastogenesis and adipogenesis in bone marrow mesenchymal stem cells (BMSCs) remains unclear. We found that ALG5 was significantly downregulated in BMSCs from osteoporotic specimens.
View Article and Find Full Text PDFAAV-based gene delivery of antimicrobial peptides to combat drug-resistant pathogens.
Appl Environ Microbiol
January 2025
Animal Sciences Research Center, Division of Animal Sciences, University of Missouri, Columbia, Missouri, USA.
Antimicrobial peptides (AMPs) have emerged as potential alternatives to conventional antibiotics due to their novelty and multiple mechanisms of action. Because they are peptides, AMPs are amenable to bioengineering and suitable for cloning and expression at large production scales. However, the efficient delivery of AMPs is an unaddressed issue, particularly due to their large size, possible toxicities, and the development of adverse immune responses.
View Article and Find Full Text PDFTFE3-mediated neuroprotection: Clearance of aggregated α-synuclein and accumulated mitochondria in the AAV-α-synuclein model of Parkinson's disease.
Genes Dis
March 2025
Growth, Development, and Mental Health of Children and Adolescence Center, Pediatric Research Institute, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.
Parkinson's disease (PD) is a neurodegenerative disorder characterized by fibrillar neuronal inclusions containing aggregated α-synuclein (α-Syn). While the pathology of PD is multifaceted, the aggregation of α-Syn and mitochondrial dysfunction are well-established hallmarks in its pathogenesis. Recently, TFE3, a transcription factor, has emerged as a regulator of autophagy and metabolic processes.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!