title: Polymers for improving the in vivo transduction efficiency of AAV2 vectors.
abstract: BACKGROUND
  Adeno-associated virus has attracted great attention as vehicle for body-wide gene delivery. However, for the successful treatment of a disease such as Duchenne muscular dystrophy infusion of very large amounts of vectors is required. This not only raises questions about the technical feasibility of the large scale production but also about the overall safety of the approach. One way to overcome these problems would be to find strategies able to increase the in vivo efficiency.
  
  
  METHODS
  Here, we investigated whether polymers can act as adjuvants to increase the in vivo efficiency of AAV2. Our strategy consisted in the pre-injection of polymers before intravenous administration of mice with AAV2 encoding a murine secreted alkaline phosphatase (mSeAP). The transgene expression, vector biodistribution and tissue transduction were studied by quantification of the mSeAP protein and real time PCR. The injection of polyinosinic acid and polylysine resulted in an increase of plasmatic mSeAP of 2- and 12-fold, respectively. Interestingly, polyinosinic acid pre-injection significantly reduced the neutralizing antibody titer raised against AAV2.
  
  
  CONCLUSIONS
  Our results show that the pre-injection of polymers can improve the overall transduction efficiency of systemically administered AAV2 and reduce the humoral response against the capsid proteins.
authors.affiliation: Research Department, Genethon, Evry, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Moulay
authors.forename: Sylvie
authors.initials: S
authors.lastname: Boutin
authors.forename: Carole
authors.initials: C
authors.lastname: Masurier
authors.forename: Daniel
authors.initials: D
authors.lastname: Scherman
authors.forename: Antoine
authors.initials: A
authors.lastname: Kichler
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000229:Dependovirus / Q000235:genetics*; D005260:Female; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D011069:Poly I / Q000378:metabolism; D011107:Polylysine / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014161:Transduction, Genetic; D019076:Transgenes
chemical_list: D011108:Polymers; D011107:Polylysine; D011069:Poly I; D000469:Alkaline Phosphatase