EFFICIENT IN-VIVO TRANSDUCTION OF THE NEONATAL MOUSE-LIVER WITH PSEUDOTYPED RETROVIRAL VECTORS

Ideal methods for human gene therapy will eventually include direct ge ne transfer to defective tissues in a patient in vivo. Toward that goa l, 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 direc t injection into the liver parenchyma. We have found that a single per cutaneous injection of small volumes of vectors into the newborn mouse liver leads to transduction of at least 25-30% of the hepatocytes thr oughout the liver, as judged by in situ staining of liver sections for beta-gal activity at 4 weeks after injection. We have demonstrated th at stable levels of HBsAg were also detected in the circulation of inj ected mice up to 4 months after HBsAg-vector injection. We suggest tha t the high efficiency of in vivo transduction in the neonatal liver an d subsequent stable transgene expression by high-titer pseudotyped ret roviral vectors in the absence of an invasive partial