Peroral gene therapy of lactose intolerance using an adeno-associated virus vector

Nat Med. 1998 Oct;4(10):1131-5. doi: 10.1038/2625.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Blood Glucose / analysis
  • Body Weight
  • Dependovirus / genetics*
  • Genetic Therapy / methods*
  • Genetic Vectors*
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / virology
  • Lactase
  • Lactose / metabolism
  • Lactose Intolerance / therapy*
  • Rats
  • Transformation, Genetic
  • Transgenes
  • beta-Galactosidase / deficiency
  • beta-Galactosidase / genetics*


  • Blood Glucose
  • Lactase
  • beta-Galactosidase
  • Lactose