title: Strategies to circumvent humoral immunity to adeno-associated viral vectors.
abstract: BACKGROUND
  Recent success in gene therapy of certain monogenic diseases in the clinic has infused enthusiasm into the continued development of recombinant adeno-associated viral (AAV) vectors as next-generation biologics. However, progress in clinical trials has also highlighted the challenges posed by the host humoral immune response to AAV vectors. Specifically, while pre-existing neutralizing antibodies (NAbs) limit the cohort of eligible patients, NAb generation following treatment prevents vector re-dosing.
  
  
  METHODS
  In this review, we discuss a spectrum of complementary strategies that can help circumvent the host humoral immune response to AAV.
  
  
  CONCLUSIONS
  Specifically, we present a dual perspective, that is, vector versus host, and highlight the clinical attributes, potential caveats and limitations as well as complementarity associated with the various approaches.
authors.affiliation: University of North Carolina, Gene Therapy Center , CB#7352, Thurston Building, Chapel Hill, NC 27599 , USA.
authors.forename: Longping V
authors.initials: LV
authors.lastname: Tse
authors.forename: Sven
authors.initials: S
authors.lastname: Moller-Tank
authors.forename: Aravind
authors.initials: A
authors.lastname: Asokan
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000235:genetics / Q000276:immunology; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000628:therapy; D000229:Dependovirus / Q000235:genetics / Q000276:immunology*; D015316:Genetic Therapy / Q000379:methods / Q000639:trends; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D006801:Humans; D056724:Immunity, Humoral / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing
keywords: adeno-associated virus; capsid; humoral immune response; neutralizing antibody; recombinant adeno-associated viral vectors