Retargeting mobile group II introns to repair mutant genes.

Journal Article (Journal Article)

Retroposable elements such as retroviral and lentiviral vectors have been employed for many gene therapy applications. Unfortunately, such gene transfer vectors integrate genes into many different DNA sequences and unintended integration of the vector near a growth-promoting gene can engender pathological consequences. For example, retroviral vector-mediated gene transfer induced leukemia in 2 of 11 children treated for severe combined immunodeficiency, raising significant safety issues for gene transfer strategies that cannot be targeted to specific sequences. Here, we examine the use of a mobile retroposable genetic element that can be targeted to introduce therapeutic sequences site specifically into mutant genes. The data demonstrate that the mobile group II intron from Lactococcus lactis can be targeted to insert into and repair mutant lacZ (approved gene symbol GLB1) and beta-globin (approved gene symbol HBB) genes with high efficiency and fidelity in model systems in bacteria. These results suggest that these mobile genetic elements represent a novel class of agents for performing targeted genetic repair.

Full Text

Duke Authors

Cited Authors

  • Jones, JP; Kierlin, MN; Coon, RG; Perutka, J; Lambowitz, AM; Sullenger, BA

Published Date

  • May 2005

Published In

Volume / Issue

  • 11 / 5

Start / End Page

  • 687 - 694

PubMed ID

  • 15851007

International Standard Serial Number (ISSN)

  • 1525-0016

Digital Object Identifier (DOI)

  • 10.1016/j.ymthe.2005.01.014


  • eng

Conference Location

  • United States