title: Impact of natural IgM concentration on gene therapy with adenovirus type 5 vectors.
abstract: Natural IgM inhibits gene transfer by adenovirus type 5 (Ad5) vectors. We show that polyreactive natural IgM antibodies bind to Ad5 and that inhibition of liver transduction by IgM depends on Kupffer cells. By manipulating IgM concentration in vivo, we demonstrate that IgM inhibits liver transduction in a concentration-dependent manner. We further show that differences in natural IgM between BALB/c and C57BL/6 mice contribute to lower efficiency of Ad5 gene transfer in BALB/c mice.
authors.affiliation: Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Qiu
authors.affiliation: Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: Zhili
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Tian
authors.affiliation: Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: Rituparna
authors.initials: R
authors.lastname: Moitra
authors.affiliation: Experimental Medicine Section, Laboratory of Sensory Biology, National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland, USA.
authors.forename: Sreenivasulu
authors.initials: S
authors.lastname: Gunti
authors.affiliation: Experimental Medicine Section, Laboratory of Sensory Biology, National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland, USA.
authors.forename: Abner L
authors.initials: AL
authors.lastname: Notkins
authors.affiliation: Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA Andrew.Byrnes@FDA.HHS.gov.
authors.forename: Andrew P
authors.identifier: http://orcid.org/0000-0003-1135-2629
authors.initials: AP
authors.lastname: Byrnes
mesh_terms: D000256:Adenoviridae / Q000235:genetics* / Q000502:physiology; D000818:Animals; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics* / Q000502:physiology; D007075:Immunoglobulin M / Q000097:blood*; D008099:Liver / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014161:Transduction, Genetic
chemical_list: D007075:Immunoglobulin M