title: Cutting edge: treatment of complement regulatory protein deficiency by retroviral in vivo gene therapy.
abstract: Gene therapy is an attractive means to replace a deficient or defective protein. Using a murine retroviral vector, we provide an example of reconstituting a C regulator by neonatal in vivo gene transfer. The fusion gene containing the mouse C receptor 1-related gene/protein y (Crry) and a single chain Ab fragment with specificity for mouse glycophorin A was placed under transcriptional control of a liver-specific promoter. Shortly after birth, Crry KO mice were injected with the retroviral vectors. Protein expression progressively increased over the next 6-8 wk after which an equilibrium was established. Coating levels on RBCs were obtained that inhibited C activation similar to wild-type cells and remained constant for > 1 year. Thus, gene therapy with targeted regulators represents a treatment option to provide a long-term and sustained protein supply for the site-specific blockade of undesirable complement activation.
authors.affiliation: Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110, USA.
authors.forename: Dirk
authors.initials: D
authors.lastname: Spitzer
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Wu
authors.forename: Xiucui
authors.initials: X
authors.lastname: Ma
authors.forename: Lingfei
authors.initials: L
authors.lastname: Xu
authors.forename: Katherine P
authors.initials: KP
authors.lastname: Ponder
authors.forename: John P
authors.initials: JP
authors.lastname: Atkinson
mesh_terms: D000818:Animals; D003167:Complement Activation / Q000187:drug effects; D004912:Erythrocytes / Q000276:immunology; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000627:therapeutic use; D006021:Glycophorins / Q000276:immunology; D007128:Immunoglobulin Fragments / Q000008:administration & dosage / Q000235:genetics; D008099:Liver; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009928:Organ Specificity; D011951:Receptors, Complement / Q000172:deficiency* / Q000235:genetics; D017463:Receptors, Complement 3b; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage; D012190:Retroviridae
chemical_list: C081470:Cr1l protein, mouse; D006021:Glycophorins; D007128:Immunoglobulin Fragments; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D011993:Recombinant Fusion Proteins