title: VP22 and cytosine deaminase fusion gene modified tissue-engineered neural stem cells for glioma therapy.
abstract: OBJECTIVE
  The herpes simplex virus type 1 tegument protein VP22 has the remarkable property of intercellular trafficking, thus making it a promising tool for improving gene transfer efficiency.
  
  
  METHODS
  To investigate whether the fusion of VP22 to the cytosine deaminase (CD) suicide gene could enhance the therapeutic efficiency of neural stem cells (NSCs) in the treatment for C6 glioma, the lentiviral vectors pHIV-VP(22)-EGFP, pHIV-CD, and pHIV-VP(22)-CD were constructed based on the pHIV-EGFP vector. After packaging, vectors were transduced into rat NSCs.
  
  
  RESULTS
  Fluorescence-activated cell sorting analysis revealed that the fusion of VP22-EGFP increased the expression rate of EGFP in NSCs compared with lenti-EGFP transduced cells. Under incubation with the prodrug 5-fluorocytosine (5-FC), the survival rates of C6 cells co-cultured with NSCs/VP(22)-CD (NSCs transduced with lenti-VP(22)-CD) decreased tremendously compared with those of C6 and NSCs/CD. Similar results were also observed in vivo; a significant reduction in tumor volumes in C6 glioma-bearing rats was observed in the NSCs/VP(22)-CD therapy group when compared with other control groups.
  
  
  CONCLUSIONS
  Our results reveal that VP22 increases the transduction efficiency of lentivirus into NSCs and enhances the therapeutic efficacy of CD-engineered rat NSCs in the treatment for C6 glioma, demonstrating that VP22 might be a useful tool for the gene therapy of engineered NSCs and providing a potential novel strategy for enhancing the effectiveness of gene therapy in other diseases.
authors.affiliation: Brain Tumor Research Center, Department of Neurosurgery, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Tiantan Xili 6, Chongwen District, Beijing 100050, People's Republic of China.
authors.forename: Guishan
authors.initials: G
authors.lastname: Jin
authors.forename: Yiqiang
authors.initials: Y
authors.lastname: Zhou
authors.forename: Qi
authors.initials: Q
authors.lastname: Chai
authors.forename: Guidong
authors.initials: G
authors.lastname: Zhu
authors.forename: Fujian
authors.initials: F
authors.lastname: Xu
authors.forename: Fusheng
authors.initials: F
authors.lastname: Liu
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics / Q000628:therapy*; D002478:Cells, Cultured; D043525:Cytosine Deaminase / Q000008:administration & dosage / Q000235:genetics* / Q000378:metabolism; D004622:Embryo, Mammalian; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005910:Glioma / Q000235:genetics / Q000628:therapy*; D006801:Humans; D008297:Male; D058953:Neural Stem Cells / Q000378:metabolism / Q000502:physiology / Q000637:transplantation*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D023822:Tissue Engineering / Q000379:methods; D015678:Viral Structural Proteins / Q000008:administration & dosage / Q000235:genetics* / Q000378:metabolism
chemical_list: D011993:Recombinant Fusion Proteins; D015678:Viral Structural Proteins; C073413:herpes simplex virus type 1 protein VP22; D043525:Cytosine Deaminase