title: Effects of a brain-engraftable microglial cell line expressing anti-prion scFv antibodies on survival times of mice infected with scrapie prions.
abstract: We first verified that a single chain Fv fragment against prion protein (anti-PrP scFv) was secreted by HEK293T cells and prevented prion replication in infected cells. We then stably expressed anti-PrP scFv in brain-engraftable murine microglial cells and intracerebrally injected these cells into mice before or after infection with prions. Interestingly, the injection before or at an early time point after infection attenuated the infection marginally but significantly prolonged survival times of the mice. These suggest that the ex vivo gene transfer of anti-PrP scFvs using brain-engraftable cells could be a possible immunotherapeutic approach against prion diseases.
authors.affiliation: Division of Molecular Neurobiology, The Institute for Enzyme Research, The University of Tokushima, Kuramoto-cho 3-18-15, Tokushima 770-8503, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Fujita
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Mori
authors.forename: Naomi
authors.initials: N
authors.lastname: Muramatsu
authors.forename: Takahito
authors.initials: T
authors.lastname: Miyamoto
authors.forename: Masashi
authors.initials: M
authors.lastname: Yano
authors.forename: Hironori
authors.initials: H
authors.lastname: Miyata
authors.forename: Akira
authors.initials: A
authors.lastname: Ootsuyama
authors.forename: Makoto
authors.initials: M
authors.lastname: Sawada
authors.forename: Haruo
authors.initials: H
authors.lastname: Matsuda
authors.forename: Ryuji
authors.initials: R
authors.lastname: Kaji
authors.forename: Suehiro
authors.initials: S
authors.lastname: Sakaguchi
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology*; D002460:Cell Line; D005822:Genetic Vectors; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000502:physiology* / Q000637:transplantation*; D011328:Prions / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D012608:Scrapie / Q000503:physiopathology* / Q000628:therapy; D057127:Single-Chain Antibodies / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D015996:Survival Rate
chemical_list: D011328:Prions; D011994:Recombinant Proteins; D057127:Single-Chain Antibodies