title: Efficient in vivo transduction of the neonatal mouse liver with pseudotyped retroviral vectors.
abstract: Ideal methods for human gene therapy will eventually include direct gene transfer to defective tissues in a patient in vivo. Toward that goal, we have used high titer, pseudotyped retroviral vectors expressing genes for the Escherichia coli beta-galactosidase (lacZ) or hepatitis B virus surface antigen (HBsAg) to infect mouse liver by in vivo direct injection into the liver parenchyma. We have found that a single percutaneous injection of small volumes of vectors into the newborn mouse liver leads to transduction of at least 25-30% of the hepatocytes throughout the liver, as judged by in situ staining of liver sections for beta-gal activity at 4 weeks after injection. We have demonstrated that stable levels of HBsAg were also detected in the circulation of injected mice up to 4 months after HBsAg-vector injection. We suggest that the high efficiency of in vivo transduction in the neonatal liver and subsequent stable transgene expression by high-titer pseudotyped retroviral vectors in the absence of an invasive partial hepatectomy may effectively be applied to gene therapy studies in a number of human liver disease [corrected].
authors.affiliation: Department of Pediatrics, UCSD School of Medicine, La Jolla, CA 92093.
authors.forename: A
authors.initials: A
authors.lastname: Miyanohara
authors.forename: J K
authors.initials: JK
authors.lastname: Yee
authors.forename: K
authors.initials: K
authors.lastname: Bouic
authors.forename: P
authors.initials: P
authors.lastname: LaPorte
authors.forename: T
authors.initials: T
authors.lastname: Friedmann
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D005069:Evaluation Studies as Topic; D015967:Gene Expression Regulation, Viral; D005822:Genetic Vectors / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics / Q000493:pharmacokinetics; D006514:Hepatitis B Surface Antigens / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D007267:Injections; D008099:Liver / Q000378:metabolism / Q000821:virology; D008562:Membrane Glycoproteins; D051379:Mice; D008979:Moloney murine leukemia virus / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis* / Q000235:genetics; D014162:Transfection / Q000379:methods*; D014721:Vesicular stomatitis Indiana virus / Q000737:chemistry; D014759:Viral Envelope Proteins; D001616:beta-Galactosidase / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C028391:G protein, vesicular stomatitis virus; D006514:Hepatitis B Surface Antigens; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins; D001616:beta-Galactosidase