title: Recombinant AAV serotype 1 transduction efficiency and tropism in the murine brain.
abstract: Recombinant adeno-associated virus serotype 2 (rAAV2) vectors have shown promise as therapeutic agents for neurologic disorders. However, intracerebral administration of this vector leads to preferential transduction of neurons and a restricted region of transgene expression. The recently developed rAAV vectors based upon nonserotype 2 viruses have the potential to overcome these limitations. Therefore, we directly compared a rAAV type 1 to a type 2 vector in the murine brain. The vectors were engineered to carry identical genomes (AAV2 terminal repeat elements flanking an enhanced green fluorescent protein expression cassette) and were administered by stereotaxic-guided intracerebral injection. We found that the rAAV1 vector (rAAV1-GFP) had a 13- to 35-fold greater transduction efficiency than that of the rAAV2 vector (rAAV2-GFP). Also, rAAV1-transduced cells were observed at a greater distance from the injection site than rAAV2-transduced cells. Neurons were the predominant cell type transduced by both vector types. However, in contrast to rAAV2-GFP, rAAV1-GFP was capable of transducing glial and ependymal cells. Thus, rAAV1-based vectors have biologic properties within the brain distinct from that of rAAV2. These differences might be capitalized upon to develop novel gene transfer strategies for neurologic disorders.
authors.affiliation: Center for Gene Therapy, Columbus Children's Research Institute, Columbus, OH, USA.
authors.forename: C
authors.initials: C
authors.lastname: Wang
authors.forename: C-M
authors.initials: CM
authors.lastname: Wang
authors.forename: K R
authors.initials: KR
authors.lastname: Clark
authors.forename: T J
authors.initials: TJ
authors.lastname: Sferra
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000821:virology*; D000229:Dependovirus / Q000145:classification / Q000235:genetics*; D004805:Ependyma / Q000378:metabolism / Q000821:virology; D015870:Gene Expression; D005818:Genetic Engineering; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000235:genetics; D049452:Green Fluorescent Proteins; D007276:Injections, Intraventricular; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008809:Mice, Inbred C3H; D009457:Neuroglia / Q000378:metabolism / Q000821:virology; D009474:Neurons / Q000378:metabolism / Q000821:virology; D012703:Serotyping; D014161:Transduction, Genetic / Q000379:methods*
chemical_list: D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins