title: In vivo targeted delivery of CD40 shRNA to mouse intestinal dendritic cells by oral administration of recombinant Sacchromyces cerevisiae.
abstract: Short hairpin RNA (shRNA)-mediated gene regulation is a commonly used technique for gene manipulation. An efficient and safe delivery system is indispensable when shRNA is delivered into living organisms for gene therapy. Previous studies have proved that DNA and protein can be delivered into dendritic cells (DCs) by non-pathogenic Saccharomyces cerevisiae without being degraded. CD40 is closely related to apoptosis of tumor cells and some immune mechanisms. In this study, we demonstrated that recombinant yeast S. cerevisiae efficiently delivered the shRNA of immune-associated gene (CD40) into mouse intestinal DCs via oral administration. Western blot analysis of isolated intestinal DCs indicated that the inhibition of CD40 gene expression reached up to 56-91%. The secretion of cytokines such as interleukin-2 (IL-2), IL-6, IL-10, IL-12, tumor necrosis factor-α and interferon-γ in intestinal DCs had varying degrees of changes. In conclusion, we found that orally administered recombinant yeast can be used as an efficient shRNA delivery system for intestinal DC-specific gene silencing and immunomodulation in vivo.
authors.affiliation: College of Animal Science and Technology, Shaan'xi Key Laboratory of Molecular Biology for Agriculture, Northwest A&F University, YangLing, Shaan'xi, People's Republic of China.
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.affiliation: College of Animal Science and Technology, Shaan'xi Key Laboratory of Molecular Biology for Agriculture, Northwest A&F University, YangLing, Shaan'xi, People's Republic of China.
authors.forename: T
authors.initials: T
authors.lastname: Zhang
authors.affiliation: College of Animal Science and Technology, Shaan'xi Key Laboratory of Molecular Biology for Agriculture, Northwest A&F University, YangLing, Shaan'xi, People's Republic of China.
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.affiliation: College of Animal Science and Technology, Shaan'xi Key Laboratory of Molecular Biology for Agriculture, Northwest A&F University, YangLing, Shaan'xi, People's Republic of China.
authors.forename: S
authors.initials: S
authors.lastname: Shao
authors.affiliation: College of Animal Science and Technology, Shaan'xi Key Laboratory of Molecular Biology for Agriculture, Northwest A&F University, YangLing, Shaan'xi, People's Republic of China.
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
authors.affiliation: College of Animal Science and Technology, Shaan'xi Key Laboratory of Molecular Biology for Agriculture, Northwest A&F University, YangLing, Shaan'xi, People's Republic of China.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019013:CD40 Antigens / Q000037:antagonists & inhibitors* / Q000235:genetics; D003713:Dendritic Cells / Q000378:metabolism* / Q000382:microbiology; D005260:Female; D020868:Gene Silencing; D018390:Gene Targeting; D005822:Genetic Vectors / Q000008:administration & dosage*; D057809:HEK293 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000166:cytology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism; D009928:Organ Specificity; D034741:RNA, Small Interfering / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics*
chemical_list: D019013:CD40 Antigens; D035683:MicroRNAs; C534715:Mirn30d microRNA, mouse; D034741:RNA, Small Interfering