title: Heart-targeted adeno-associated viral vectors selected by in vivo biopanning of a random viral display peptide library.
abstract: Selection of targeted vectors from virus display peptide libraries is a versatile and efficient approach to improve vector specificity and efficiency. This strategy has been used to target various cell types in vitro. Here, we report the screening of an adeno-associated virus type 2 (AAV2) display peptide library in vivo to select vectors specifically homing to heart tissue after systemic application in mice. Selected library clones indicated superior specificity of gene transfer compared with wild-type AAV2, AAV9 and a heparin binding-deficient AAV2 mutant. Such targeted vectors were able to reconstitute expression of delta-sarcoglycan in the heart of adult delta-sarcoglycan knockout mice after systemic gene transfer in vivo, attesting to the therapeutic potential of this approach.
authors.affiliation: Department of Tumorvirology, German Cancer Research Center, Im Neuenheimer Feld 242, Heidelberg, Germany.
authors.forename: Y
authors.initials: Y
authors.lastname: Ying
authors.forename: O J
authors.initials: OJ
authors.lastname: Müller
authors.forename: C
authors.initials: C
authors.lastname: Goehringer
authors.forename: B
authors.initials: B
authors.lastname: Leuchs
authors.forename: M
authors.initials: M
authors.lastname: Trepel
authors.forename: H A
authors.initials: HA
authors.lastname: Katus
authors.forename: J A
authors.initials: JA
authors.lastname: Kleinschmidt
mesh_terms: D000818:Animals; D002460:Cell Line; D000229:Dependovirus / Q000235:genetics*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000821:virology; D019151:Peptide Library; D051381:Rats; D049031:Sarcoglycans / Q000235:genetics*; D014161:Transduction, Genetic
chemical_list: D019151:Peptide Library; D049031:Sarcoglycans