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ABSTRACT: To improve the expression levels of transgenes in malignant hematopoietic cells, we developed a novel adenoviral-alphavirus hybrid vector Ad5/F11p-SFV-GFP that contains a Semliki Forest Virus (SFV) replicon and chimeric fibers of Ad5 and Ad11p. Ad5/F11p-SFV-GFP infected >95% of K562, U937 or Jurkat cells and 23.65% of HL-60 cells, and led to moderate Enhanced Green Fluorescent Protein (EGFP) transgene expression intensity. The infection efficiency of Ad5/F11p-SFV-GFP in primary human leukemia cells ranged from 9.34-89.63% (median, 28.58%) at a multiplicity of infection (MOI) of 100, compared with only 3.37-44.54% (median, 10.42%) in cells infected by Ad5/F11p-GFP. Importantly, Ad5/F11p-SFV-GFP led to a significantly higher transgene expression level in primary leukemia cells, as indicated by the relative fluorescence intensity, compared to cells infected with Ad5/F11p-GFP. The increased expression of EGFP in Ad5/F11p-SFV-GFP-infected cells was associated with the accumulation of abundant subgenomic mRNA. Additionally, infection of K562, U937 or Jurkat cells by Ad5/F11p-SFV-GFP was significantly inhibited by blocking CD46 receptor; however, other factors may affect the gene-transfer efficiency of Ad5/F11p-SFV-GFP in primary leukemia cells. In conclusion, we successfully developed a novel adenoviral-alphavirus hybrid vector with RNA replicon features, which represents a promising vector for gene modifications during the production of cell-based vaccines for leukemia patients.Cancer Gene Therapy advance online publication, 5 July 2013; doi:10.1038/cgt.2013.37.
Cancer gene therapy 07/2013; · 3.13 Impact Factor
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ABSTRACT: Human acidic fibroblast growth factor (haFGF), a neurotrophin-like growth factor in the brain, plays important roles in the development, differentiation and regeneration of brain neurons, which makes it potential to treat Alzheimer's disease (AD). In this study, haFGF(14-154) and TAT-haFGF(14-154) (haFGF(14-154) fused with the cell-penetrating peptide transactivator of transcription protein transduction domain (TAT-PTD)) were intranasally administrated for 5weeks to investigate the effects on senescence-accelerated mouse prone-8 (SAMP8) mice (a mouse model of AD). Results showed that TAT-PTD could increase the concentration of haFGF in the brain significantly, and TAT-haFGF(14-154) was more effective than haFGF(14-154) in the same dosage (300μg/kg). Importantly, TAT-haFGF(14-154) improved the learning and memory abilities of SAMP8 mice in the behavioral test, and promoted the function of cholinergic system by measuring the relevant biomarkers (acetylcholine (ACh) level, acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) activities). TAT-haFGF(14-154) also significantly reduced β-amyloid protein(1-42) (Aβ(1-42)) deposits as well as the levels of Aβ soluble forms in the mice brains and prevented the neurons from apoptosis. Besides, the oxidative stress impairment in the brain and serum was also ameliorated. The results suggest that TAT-haFGF(14-154) could attenuate the disease progression of SAMP8 AD mice, and the mechanism is related to the regulation of neurons microenvironment including neurotransmitters, Aβ pathology and oxidative stress.
Neuroscience 08/2012; 223:225-37. · 3.12 Impact Factor
International Journal for Numerical Methods in Fluids 12/2011; 67(12):1993-2014. · 1.35 Impact Factor