title: Human galectin 3 binding protein interacts with recombinant adeno-associated virus type 6.
abstract: Recombinant adeno-associated viruses (rAAVs) hold enormous potential for human gene therapy. Despite the well-established safety and efficacy of rAAVs for in vivo gene transfer, there is still little information concerning the fate of vectors in blood following systemic delivery. We screened for serum proteins interacting with different AAV serotypes in humans, macaques, dogs, and mice. We report that serotypes rAAV-1, -5, and -6 but not serotypes rAAV-2, -7, -8, -9, and -10 interact in human sera with galectin 3 binding protein (hu-G3BP), a soluble scavenger receptor. Among the three serotypes, rAAV-6 has the most important capacities for binding to G3BP. rAAV-6 also bound G3BP in dog sera but not in macaque and mouse sera. In mice, rAAV-6 interacted with another protein of the innate immune system, C-reactive protein (CRP). Furthermore, interaction of hu-G3BP with rAAV-6 led to the formation of aggregates and hampered transduction when the two were codelivered into the mouse. Based on these data, we propose that species-specific interactions of AAVs with blood proteins may differentially impact vector distribution and efficacy in different animal models.
authors.affiliation: Genethon, Evry, France.
authors.forename: Jerome
authors.initials: J
authors.lastname: Denard
authors.forename: Cyriaque
authors.initials: C
authors.lastname: Beley
authors.forename: Robert
authors.initials: R
authors.lastname: Kotin
authors.forename: René
authors.initials: R
authors.lastname: Lai-Kuen
authors.forename: Stéphane
authors.initials: S
authors.lastname: Blot
authors.forename: Hervé
authors.initials: H
authors.lastname: Leh
authors.forename: Aravind
authors.initials: A
authors.lastname: Asokan
authors.forename: R Jude
authors.initials: RJ
authors.lastname: Samulski
authors.forename: Philippe
authors.initials: P
authors.lastname: Moullier
authors.forename: Thomas
authors.initials: T
authors.lastname: Voit
authors.forename: Luis
authors.initials: L
authors.lastname: Garcia
authors.forename: Fedor
authors.initials: F
authors.lastname: Svinartchouk
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D000229:Dependovirus / Q000145:classification / Q000235:genetics / Q000502:physiology*; D004285:Dogs; D015316:Genetic Therapy / Q000295:instrumentation; D005822:Genetic Vectors / Q000145:classification / Q000235:genetics / Q000502:physiology; D006023:Glycoproteins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008251:Macaca; D051379:Mice; D008810:Mice, Inbred C57BL; D011485:Protein Binding; D013045:Species Specificity; D014161:Transduction, Genetic; D016326:Extracellular Matrix Proteins
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D006023:Glycoproteins; C081856:LGALS3BP protein, human; D016326:Extracellular Matrix Proteins