Gene Targeting Disrupts Osteogenesis Imperfecta Mutation in Stem Cells

[Guest guest]

Gene Targeting Disrupts Osteogenesis Imperfecta Mutation in Stem Cells

NEW YORK (Reuters Health) Feb 20 - Using viral vectors, US researchers have

been able to target and eliminate the dominant gene mutations found in

mesenchymal stem cells from patients with osteogenesis imperfecta.

In theory, these cells could then be transplanted back into the patient for

therapeutic benefit.

Osteogenesis imperfecta is caused by mutations in the COL1A1 and COL1A2

genes that govern type I collagen production. The most severe forms of the

disorder arise from dominant mutations that disrupt the normal helical

structure of collagen.

As reported in the February 20th issue of Science, Dr. W. ,

from the University of Washington in Seattle, and colleagues created

adeno-associated virus vectors that were designed to disrupt exon 1 of the

COL1A1 gene.

With this technique, called gene targeting, they were able to disrupt the

dominant-negative mutant COL1A genes found in the stem cells of OI patients.

Moreover, the treated cells showed improved collagen production in vitro and

were able to generate bone when transplanted into mice.

" A major advantage of gene targeting is that random integration events can

be avoided or minimized, which could prevent the development of malignancies

by oncogene activation, as observed after treatment with integrating

retroviral vectors, " the authors conclude.

Science 2004;303:1198-1201.