Peroral gene therapy of lactose intolerance using an adeno-associated virus vector.
Gene therapy is usually reserved for severe and medically refractory disorders because of the toxicity, potential long-term risks and invasiveness of most gene transfer protocols. Here we show that an orally administered adeno-associated viral vector leads to persistent expression of a beta-galactosidase transgene in both gut epithelial and lamina propria cells, and that this approach results in long-term phenotypic recovery in an animal model of lactose intolerance. A gene 'pill' associated with highly efficient and stable gene expression might be a practical and cost-effective strategy for even relatively mild disorders, such as lactase deficiency.
During
M J
MJ
Department of Molecular Medicine, University of Auckland School of Medicine, New Zealand. Matthew.During@mail.tju.edu
Xu
R
R
Young
D
D
Kaplitt
M G
MG
Sherwin
R S
RS
Leone
P
P
D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D000229:Dependovirus / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D007413:Intestinal Mucosa / Q000378:metabolism / Q000821:virology; D043322:Lactase; D007785:Lactose / Q000378:metabolism; D007787:Lactose Intolerance / Q000628:therapy*; D051381:Rats; D014170:Transformation, Genetic; D019076:Transgenes; D001616:beta-Galactosidase / Q000172:deficiency / Q000235:genetics*
D001786:Blood Glucose; D043322:Lactase; D001616:beta-Galactosidase; D007785:Lactose