title: Utility of intraperitoneal administration as a route of AAV serotype 5 vector-mediated neonatal gene transfer.
abstract: BACKGROUND
  Gene transfer into a fetus or neonate can be a fundamental approach for treating genetic diseases, particularly disorders that have irreversible manifestations in adulthood. Although the potential utility of this technique has been suggested, the advantages of neonatal gene transfer have not been widely investigated. Here, we tested the usefulness of neonatal gene transfer using adeno-associated virus (AAV) vectors by comparing the administration routes and vector doses.
  
  
  METHODS
  To determine the optimal administration route, neonates were subjected to intravenous (i.v.) or intraperitoneal (i.p.) injections of AAV5-based vectors encoding the human coagulation factor IX (hfIX) gene, and the dose response was examined. To determine the distribution of transgene expression, vectors encoding lacZ or luciferase (luc) genes were used and assessed by X-gal staining and in vivo imaging, respectively. After the observation period, the vector distribution across tissues was quantified.
  
  
  RESULTS
  The factor IX concentration was higher in i.p.-injected mice than in i.v.-injected mice. All transgenes administered by i.p. injection were more efficiently expressed in neonates than in adults. The expression was confined to the peritoneal tissue. Interestingly, a sex-related difference was observed in transgene expression in adults, whereas this difference was not apparent in neonates.
  
  
  CONCLUSIONS
  AAV vector administration to neonates using the i.p. route was clearly advantageous in obtaining robust transgene expression. Vector genomes and transgene expression were observed mainly in the peritoneal tissue. These findings indicate the advantages of neonatal gene therapy and would help in designing strategies for gene therapy using AAV vectors.
authors: Division of Genetic Therapeutics, Center for Molecular Medicine, Jichi Medical School, Tochigi, Japan.
authors: Tsuyoshi
authors: T
authors: Ogura
authors: Hiroaki
authors: H
authors: Mizukami
authors: Jun
authors: J
authors: Mimuro
authors: Seiji
authors: S
authors: Madoiwa
authors: Takashi
authors: T
authors: Okada
authors: Takashi
authors: T
authors: Matsushita
authors: Masashi
authors: M
authors: Urabe
authors: Akihiro
authors: A
authors: Kume
authors: Hiromi
authors: H
authors: Hamada
authors: Hiroyuki
authors: H
authors: Yoshikawa
authors: Yoichi
authors: Y
authors: Sakata
authors: Keiya
authors: K
authors: Ozawa