Gene therapy--treating a genetic defect by inserting corrected DNA--has not yet lived up to its promise. The major stumbling block is that, although the corrected DNA can be synthesized and inserted into a cell, no reliable way has been found of inserting it into the correct place in the cell's DNA--and correct placement is critical to proper function.
For this reason, recent studies by NIGMS grantees Drs. Alan Lambowitz and Philip Perlman, along with their colleagues at the University of Texas at Austin and the University of Texas Southwestern Medical Center at Dallas, are of particular interest to researchers seeking to develop effective gene therapy techniques. The scientists discovered that cellular elements called group II introns, which are capable of inserting themselves into DNA, do so by recognizing specific sequences. Moreover, the researchers have been able to change where an intron inserts by modifying both the intron and the target DNA sequence. This raises the possibility that the approach might be harnessed to deliver corrected DNA to a desired location.
This work builds on the discovery and characterization of RNA sequences called group I introns that can perform catalytic functions--work that led to the 1989 Nobel Prize for another NIGMS grantee, Dr. Thomas Cech. Prior to that ground-breaking work, researchers thought that only proteins could catalyze chemical reactions. Group II introns, which are also RNAs with catalytic activity, are different in structure from group I introns and appear to have multiple pathways of splicing and transposition. Whatever use is eventually made of these discoveries, the work is an important advance in understanding the many functions of catalytic RNAs.
Guo H, Zimmerly S, Perlman PS, Lambowitz AM. Group II intron endonucleases use both RNA and protein subunits for recognition of specific sequences in double-stranded DNA. EMBO J 1997;16:6835-48.
Eskes R, Yang J, Lambowitz AM, Perlman PS. Mobility of yeast mitochondrial group II introns: engineering a new site specificity and retrohoming via full reverse splicing. Cell 1997;88:865-74.
Yang J, Zimmerly S, Perlman PS, Lambowitz AM. Efficient integration of an intron RNA into double-stranded DNA by reverse splicing. Nature 1996; 381: 332-5.
Reporters may call the NIGMS Office of Communications and Public Liaison at (301) 496-7301 to obtain the name of a scientist in the NIGMS Division of Genetics and Developmental Biology who can comment on this work.
This page last reviewed on
8/9/2018 5:44 PM
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