NEW YORK (Reuters Health) - 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. David W. Russell, 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.
Source: Science 2004;303:1198-1201. [ Google search on this article ]
MeSH Headings:DNA, Recombinant: Genetic Techniques: Genetic Vectors: Investigative Techniques: Gene Transfer: Analytical, Diagnostic and Therapeutic Techniques and EquipmentCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
